4 2-Pharmacology

MODULE 4
PHARMACOLOGY
PHARMACOLOGY 1. ANATOMIC DIVISIONS OF THE NERVOUS SYSTEM
Study of drugs
Nervous System
Drugs
articles used in diagnosis, prevention, treatment, mitigation
of diseases.
Peripheral nervous Central nervous
CLASSIFICATION OF DRUGS system system
1. Diagnostic agents drugs being given primarily to determine the

cause of a disease or to confirm diagnosis
Efferent division Afferent division
Edrophonium (Tensilon®) diagnosis of Myasthenia gravis,
differentiates myasthenic from cholinergic crisis (base on the
improvement or deterioration in the muscle strength when the drug is
given)
Myasthenic crisis insufficient dose of the drug we are given. Autonomic system Somatic system
Radiopharmaceuticals Technetium 99m sestamibi for
Myocardial ischemia
Insulin performance of Insulin Tolerance Test to
determine reserves of growth hormone. Enteric Parasympathetic Sympathetic
2. Replenishers given to supplement lacking endogenous

substances
Cyanocobalamin Mx of Pernicious Anemia (B12 Nervous System
deficiency); characterized by the presence of auto antibodies that is Central Nervous System Peripheral Nervous System
directed against their own cells, these antibodies destroy an important Afferent Neurons
cell which is responsible for producing a substance for Vitamin B12 Sensory enter the
absorption in the Ilium. Cyanocobalamin is given IM in as much as CNS
there is lack of the intrinsic factor in Pernicious Anemia that will allow
the absorption of B12 in the GIT.
Insulin for Insulin-requiring DM Efferent Neurons
Motor leave the CNS
3. Functional modifiers alter normal physiologic function
processes. Efferent Neurons
Analgesics alter pain perception
Antipyretic alter effects of endogenous pyrogens a. Somatic Nervous System
BIGGEST CLASS OF DRUGS Single neuron
Carries impulses going to the organs that are voluntarily
4. Chemotherapeutic agents moving such as skeletal muscles
Drugs used to treat or inhibit growth of cells or proliferation of
nucleic acids that considered foreign to the body b. Autonomic Nervous System
Anti-infectives (antibacterial, antiviral, antifungal, 2-neuron set-up
antiparasitic) Carries impulses towards the organs that are independent or
Anti-neoplastic involuntarily moving such cardiac muscles, smooth muscles
and exocrine glands
BRANCHES OF PHARMACOLOGY
Ganglion
1. Pharmacodynamics (PD)
What the drug does to the body
Study of the biochemical and physiologic effects of drugs in Pre-ganglion Post-ganglion
biological systems, and the mechanism by which these
effects are produced
Effector
2. Pharmacokinetics (PK) CNS
What the body does to the drug
Study of processes a drug undergoes as it reaches and Ganglion collection of neuron cell bodies in the PNS
leaves the biological site of action
2. SYNAPTIC NEUROTRANSMISSION
3. Pharmacotherapeutics
Study of rational use of drugs in the management of Nervous system is not a continuous system
diseases Gaps are present
between 2 neurons
(See Biopharmaceutics) between a neuron and an effector
AUTONOMIC PHARMACOLOGY Parts of the Synapse
A. ANATOMY AND PHYSIOLOGY OF THE ANS - Synthesis, storage and

release of neurotransmitters
- Metabolizing enzymes
1. Anatomic Divisions of the Nervous System - Auto receptors
1. Pre-synapse
2. Synaptic Neurotransmission
3. Synaptic Cleft
3. Subdivisions of Autonomic Nervous System - Metabolizing enzymes
2. Post-synapse - Majority of receptors
- Metabolizing enzymes
Module 4 Pharmacology Page 1 of 33 RJAV 2022

Steps Functional Difference
Neurotransmitters carry information from the pre-synaptic sending neuron SANS PANS
to the post-synaptic receiving cell. Synapses are usually formed between Fight/ Flight Rest/ Digest
nerve terminals axon terminals on the sending neuron and the cell body or Heart Tachycardia Bradycardia
dendrites of the receiving neuron. Eyes Mydriasis Miosis
A single axon can have multiple branches, allowing it to make synapses on
Lungs Bronchodilation Bronchoconstriction
various postsynaptic cells. Similarly, a single neuron can receive thousands of
Intestine Ileus Bowel Movement
synaptic inputs from many different presynaptic sending neurons.
Gall
Inside the axon terminal of a sending cell are many synaptic vesicles. These Urinary Retention Urination
bladder
are membrane-bound spheres filled with neurotransmitter molecules. There is
a small gap between the axon terminal of the presynaptic neuron and the Palms and
Sweating Generalized
membrane of the postsynaptic cell, and this gap is called the synaptic cleft. Soles
Pre-synaptic Axon terminal B. SYMPATHETIC DRUGS

cell
Synaptic vehicle 1. Natural Catecholamines
Neurotransmitter
Voltage-gated
2. Receptors
Ca2+ channel
3. Sympathomimetics
Synaptic Receptor for
neurotransmitter
3. Sympatholytics
cleft
(ligand-gated ion
channel) 1. NATURAL CATECHOLAMINES
Post-synaptic cell
Endogenous self-made; they are being produced inside the
When an action potential, or nerve impulse, arrives at the axon terminal, it body
activates voltage-gated calcium channels in the cell membrane. Ca2+ which is Norepinephrine, Epinephrine, Dopamine
present at a much higher concentration outside the neuron than inside, rushes
into the cell. The Ca2+
allows synaptic vesicles to fuse with the axon terminal membrane, releasing Locations:
neurotransmitter (Exocytosis) into the synaptic cleft.
a. Sympathetic post-ganglion particularly NE
1. Action potential reaches
Action axon terminal and b. Adrenal medulla NE, Epi
potential depolarizes membrane
c. Brain NE, Dopamine
arrives 2. Voltage-gated Ca2+
channel is open and Ca2+
flows in Steps
3. Ca2+ influx triggers
synaptic vesicles to release
neurotransmitter
4. Neurotransmitter binds to
receptors on target cell (in
this case, causing positive
ions to flow in
depolarization
more likely to fire action potential
The molecules of neurotransmitter diffuse across the synaptic cleft and bind to
receptor proteins on the postsynaptic cell. Activation of postsynaptic receptors
leads to the opening or closing of ion channels in the cell membrane. This may
be depolarizing make the inside of the cell more positive or
hyperpolarizing make the inside of the cell more negative depending on
the ions involved. Drugs
3. SUBDIVISIONS OF AUTONOMIC NERVOUS SYSTEM
3 Major Subdivisions:
Enteric Nervous System

Sympathetic Nervous System
Parasympathetic Nervous System
Anatomical Difference
Sympathetic NS Parasympathetic NS
Origin/ Roots of Fibers
Thoraco-Lumbar NS Cranio-Sacral NS
T1 T12 Cranial: 3,7,9,10
Tyramine
L1 L4 S2 S4
Ephedrine
Length of Fibers
Amphetamine
Short: Pre-ganglionic neuron Long: Pre-ganglionic neuron Angiotensin II
Long: Post-ganglionic neuron Short: Post-ganglionic neuron -latrotoxin
Location of Ganglion
Near the CNS Near the Effector organ
Neurotransmitters
Ach: Pre-ganglionic neuron Ach: Pre-ganglionic neuron & Guanethidine
NE: Post-ganglionic neuron Post-ganglionic neuron Guanadrel
Receptors Bretylium
Ganglia: Nicotinic Ganglia: Nicotinic
Effector: , , Dopa Effector: Muscarinic, Nicotinic

Termination Skeletal muscles
Increased inward conductance
Cell membranes
to K+ ions = Hypokalemia
Neuromuscular endplates Contraction = Tremors
3) Receptors:
Target Response
Adipocytes Lipolysis
Dopaminergic Receptors:
Dopaminergic1 Receptor (Gs-linked)

Target Response
Renal and Splanchnic Blood
vessels
Dopaminergic2 Receptor (Gi-linked)

Target Response
Peripheral (GI tract) Relaxation (ileus; no peristalsis)
Perception and behavior
Central (Brain)
Modulation of motor activity
The vesicular monoamine transporter (VMAT) is responsible for the transport

3. SYMPATHOMIMETICS
of catecholamines to the storage vesicles, maintaining their cytosolic
concentration low. After catecholamine release to the synaptic cleft,
catecholamines are reuptaken to the presynaptic terminal by noradrenaline Adrenergic Agonists
transporter (NET), and/or taken to extraneuronal cells by the extraneuronal Mimicry
transporters. The most important extraneuronal transporter for catecholamines
is extraneuronal monoamine transporter (EMT). Catecholamines are Classifications
metabolized by intracellular enzymes. Monoamine oxidase (MAO) is located in
the outer membrane of mitochondria in neurons and in extraneuronal cells. Based on Catecholamines
Catechol-O-methyl transferase (COMT) is located at extraneuronal cells. Both Chemistry Non-catecholamines
enzymes (COMT and MAO) are the main responsible for the metabolism of
catecholamines. The enzymatic process leads to the formation of several
metabolites. To exert their actions, the catecholamines and other Based on Direct-acting
neurotransmitters in the synaptic cleft bind to different pre-and postsynaptic Mechanism of
receptors. Such binding leads to alterations in the postsynaptic cell and
Indirect-acting
Action Mixed-acting
activation of intracellular pathways through G proteins. In presynaptic neurons,
catecholamines bind to autoreceptors and activate feed-back responses that
change their own release.
BASED ON CHEMISTRY
2. RECEPTORS
Catecholamines
Catechol
3,4-dihydroxybenzene group
Dopaminergic (D) Receptors High potency in activating and receptors

Metabolized by MAO and COMT
Alpha ( Do not penetrate the CNS
Alpha1 ( 1) Receptors
Target (Smooth muscle) Response
Vascular smooth muscle
Bladder, trigone & sphincter females
Urinary Retention
Prostatic smooth muscles males
Radial muscles (iris) Contraction = mydriasis
Contraction (piloerection) =
Pilomotor smooth muscles (skin)
goosebumps
Alpha2 ( 2) Receptors
Target Response
Pre-synaptic alpha 2 (Gi-linked)
from the vesicles)
Central Sedation
Peripheral blood vessels Non-catecholamines
No catechol
: Not metabolized by MAO and COMT
Longer half-lives
1) Receptors (Gs-linked) Administered orally
Target Response
(+) Inotropism
Force of contraction
Heart (Cardiac myocytes) (+) Chromotopism
Heart rate
(+) Dromotropism
AV nodal conduction
Renin secretion
Kidneys
RAAS activation =
Renal Juxtaglomerular Apparatus
Increased BP
2)
Receptors (Gs-linked)
Target Response
Smooth muscles
Bronchi Bronchodilation
Uterus Relaxation (tocolysis)
Blood vessels (skeletal muscles) Vasodilation

BASED ON MOA - Management of preterm labor (tocolytics)
- Adjunct in the management of
Direct-acting: hyperkalemia
- Non-selective
Toxic effects :
binds and activate more than 1 general type of - Tremors
adrenergic receptor - Hyperkalemia
- Selective D1-Selective - Fenoldopam (Corlopam ®)
binds and activates 1 general type of adrenergic Agonists - Used as an alternative for
receptor hypertensive crisis
Non-selective: Indirect-acting
Epinephrine: - Anaphylaxis, anaphylactic shock,
1 1 2 anaphylactoid reaction Releasers Reuptake inhibitors
- Cardiac stimulant Enhances exocytosis of NE - Tricyclic antidepressants
- Local vasoconstrictor (+ Lidocaine) - Centrally acting
- Galucoma: Dipivefrin lower intraocular - Tyramine - Cocaine
pressure - Ephedrine - Local Anesthetic
Norepinephrine: - Septic Shock - Amphetamine - Atomoxetine
1 1 - Methamphetamine - ADHD
Dopamine: - Cardiogenic shock (alternative) - Sibutramine
1 1, D1 - Acute Heart Failure - Methylphenidate - Obesity
Toxic Effects: - ADHD (1st line)
- 1 - Phenmetrazine
- 1 - Anorexiant
- Modafinil
Selective - Narcolepsy
1-selective Constrictor Agents:
Agonists - Phenylephrine Mixed-acting
- Methoxamine Ephedrine For Narcolepsy
- Propyhexedrine Mephentermine and Metaraminol For Hypotension
- Tetrahydrozoline Phenylpropanolamine For Nasal congestion
- Oxymetazoline
- Nafazoline
4. SYMPATHOLYTICS
Clinical uses
- Nasal & Ophthalmic congestion Adrenergic Antagonists
- Hypotension Relaxation (blocking alpha receptors)
- Local vasoconstrictions Cardiac depression (blocking beta receptors)
Toxic Effects: Classifications
- Local:
- Rhinitis medicamentosa or rebound Direct-Acting Alpha Blockers
congestion (do not use for more than Beta Blockers
3 days)
- Systemic: Peripherally- Adrenergic Neuronal
- Hypertension Acting Blockers
- Urinary retention (Benign prostatic
hyperplasia)
- Tolerance (do not use for more than DIRECT-ACTING
5days)
2-selective Anti-hypertensive: Alpha Blockers
Agonists - Clonidine 1 2 Nonselective, Irreversible, Noncompetitive Phenoxybenzamine
- hypertensive crisis (rapid acting) 1 2 Nonselective, Reversible Phentolamine
- alternative for ADHD Selective, Reversible Yohimbine
2
- Toxic effects: Clonidine withdrawal-
2 Adrenergic Selective, Reversible Prazosin
induced HTN
Doxazosin
- Methyldopa
Terazosin
- FDA approved for Pregnant women
Tamsulosin
- Toxic effects: Sedation,
Alfuzosin
Hepatotoxicity, (+) Coombs test
- Guanfacine centrally acting
- Guanabenz centrally acting Clinical Uses:
Phenoxybenzamine Pheochromocytoma
Anti-glaucoma - (pre-surgical)
- Apraclonidine - a catecholamine secreting tumor of
- Brimonidine cells derived from the adrenal
Non-selective - Isoproterenol medulla
Agonists - Alternative during shock states - used prior to surgical removal of
- Management of Acute Heart Failure tumor to prevent hypertensive crisis
- Inotropic
1-selective - Dobutamine Mastocytosis (H-blockade)
Agonists - First line for cardiogenic shock - too much masts cells that store
- Management of Acute Heart Failure histamine
- Pharmacologic stress test (with
dipyridamole) Carcinoid Tumor (5-HT blockade)
2-selective Bronchodilators - abnormal high levels of serotonin
Agonists - SABAs (Salbutamol/Albuterol, Terbutaline, Phentolamine Pheochromocytoma
Pirbuterol, Metaproterenol) - (during surgical)
- LABAs (Salmeterol, Formoterol,
Bambuterol, Indacaterol) Raynaud Syndrome
Tocolytics Accidental local infiltration of alpha agonists and

- Ritodrine sympathomimetic poisoning
- Isoxsuprine
- Terbutaline (off-label use) Erectile Dysfunction
- Locally administered
Clinical Uses : Yohimbine Erectile dysfunction
- Management of bronchial asthma and Prazosin HTN: Prazosin, Doxazosin, Terazosin
COPD (bronchodilators) Doxazosin - Vasodilators

Terazosin Selective Beta 1 antagonist
Tamsulosin Benign prostatic hyperplasia (BPH): Tamsulosin, Useful in hypertensive patients with impaired pulmonary
Alfuzosin Alfuzosin function
- Used as an alternative to surgery
First line therapy for chronic stable angina
Toxicities: Acebutolol and Pindolol
Reflex Tachycardia Beta blockers with ISA are effective in hypertensive
Orthostatic Hypotension patients with moderate bradycardia, because a further
Nausea and Vomiting decrease in heart rate is less pronounced in these
drugs.
Beta Blockers
Not used for stable angina and arrhythmias due to their
Effects:
(-) Dromotropism = Lesser conduction velocity partial agonist effect
(-) Inotropism = Lesser force
(-) Chronotropism = Lesser rate Labetalol
Classes: Alternative to methyldopa in the treatment of
Based on Non-selective Nadolol pregnancy-induced hypertension
selectivity Sotalol Used in hypertensive emergencies (it can rapidly lower
Timolol blood pressure)
Propranolol
1-Selective or Cardioselective Metoprolol
Toxicities:
Acebutolol
Celiprolol Augmentation of hypoglycemia
Betaxolol Bradycardia; AV Block
Atenolol Dyslipidemia
Bisporolol Bronchoconstriction (Asthma)
Esmolol
Based on their Beta blocker with Intrinsic Celiprolol PERIPHERALLY-ACTING
miscellaneous Sympathomimetic Activity (ISA) Carteolol
action - 1 Labetalol
2 Acebutolol Adrenergic Neuronal Blockers
agonism effect Penbutolol Inhibits storage Inhibits release
Beta blocker with Membrane Pindolol
Stabilizing Action ( MSA ) Propranolol bind to the receptor
- they possess local Acebutolol Reserpine Bretylium
anesthetic effect Labetalol - Guanadrel
- not instilled in the eyes Metoprolol regulators like serotonin Guanethedine
- not prepared as and NE - Pharmacologic
ophthalmic drops due to - sympathectomy
inhibition of blinking characterized by mark
reflex resulting to drying postural hypotension;
of the eyes leading to impaired ejaculation
corneal injury
Beta blocker with Alpha-1 Carvedilol C. PARASYMPATHETIC DRUGS
blocking effect Labetalol
- Vasodilating effect
Most cardio selective Beta Nebivolol 1. Acetylcholine
blocker among Beta blockers
- it has a vasodilating 2. Cholinoreceptors
effect due to increase of
Nitric oxide 3. Parasympathomimetics
Indications: 3. Parasympatholytics
Cardiovascular diseases
1st line agent in the management of Hypertension in 1. ACETYLCHOLINE
patients with history of post myocardial infarction
Treatment of angina pectoris (CSAP) Locations:
Management of congestive heart failure: Bisoprolol, a. Vesicle
Metoprololsuccinate, Carvedilol, Nebivolol b. Cholinergic Post gangllion
Arrhythmia: Class II agents c. Central Nervous System
d. Skeletal Muscles
Propranolol e. Stomach
Useful in chronic management of Stable Angina
1st line agent in the management of hypertension in Steps
patients with a history of post myocardial infarction
*protective effect on the myocardium; can protect a
patient against a second heart attack
(prophylaxis)reduces infarct size and hasten recovery
Prophylaxis in acute migraine headache
Management of sympathetic symptoms of
Hyperthyroidism
Protects against serious cardiac arrhythmias (due to
thyroid storm)
Management of Stage Fright
Nadolol and Timololmore potent than Propranolol

Nadolol very long duration of action
Timolol reduces the production of aqueous humor in
the eye | topically used in the treatment of chronic open-
angle glaucoma (Timolol and Betaxolol) | decreases the
secretion of aqueous humor by the ciliary body
* note: Pilocarpine is still the DOC for emergency
lowering of IOP (acute glaucoma)

Choline is transported into the presynaptic nerve terminal by a sodium- Alkaloids
dependent choline transporter (CHT). This transporter can be inhibited by Non selective Arecholine
hemicholinium drugs. In the cytoplasm, acetylcholine is synthesized from
Muscarinic-selective Muscarine
choline and acetyl-CoA (AcCoA) by the enzyme choline acetyltransferase
(ChAT). Acetylcholine is then transported into the storage vesicle by a second Pilocarpine
carrier, the vesicle-associated transporter (VAT), which can be inhibited by Nicotinic-selective Nicotine
vesamicol. Peptides (P), adenosine triphosphate (ATP), and proteoglycan are Lobeline
also stored in the vesicle. Release of transmitter occurs when voltage- Varenicline
sensitive calcium channels in the terminal membrane are opened, allowing an
influx of calcium. The resulting increase in intracellular calcium causes fusion Indications
of vesicles with the surface membrane and exocytotic expulsion of Betanechol - Management of Urinary retention
acetylcholine and cotransmitters into the junctional cleft This step can be - Post-operative abdominal distention and gastric
blocked by botulinum t atony
by the enzyme acetylcholinesterase. Receptors on the presynaptic nerve
Metacholine - Pulmonary challenge test (provocative test for
ending modulate transmitter release. SNAPs, synaptosome-associated
bronchial hyperactivity)
proteins; VAMPs, vesicle-associated membrane proteins.
Pilocarpine - Reduces intraocular pressure in open angle and
narrow angle glaucoma
Drugs: - Binds preferentially at muscarinic receptors
Acetylcholine - Produce miosis in ophthalmic surgery
Hemicholinium block entry of choline Nicotine - Smoking cessation
Vesaminol inhibits storage of ACh into the vesicle Lobeline
Botulinum toxin inhibit exocytosis of Ach Varenicline
Anticholinesterases
Irreversible Inhibitors
2. CHOLINOCEPTORS Organophosphates Echothiophate
Malathion
Parathion
Muscarinic (M)
Nerve Gases:
Sarin
Nicotinic (N) Tabbun
Soman
Muscarinic (M) Receptors:

INDIRECT ACTING
Muscarinic 1 (M1) Gq - linked
Target Response
Reversible Inhibitors
Gastric gland HCl secretion
Aminoalcohol Endrophonium (Tensilon)
Carbamates Physostigmine/Eserine
Muscarinic 2 (M2) Gi - linked
Target Response Neostigmine
Heart (artria) Pyridostigmine
contractility of the atria) Ambenonium
Demecarium
Muscarinic 3 (M3) Gq - linked
Target Response CNS-acting
Exocrine Glands Secretion = Eccrine, Lacrimal, Tacrine
Salivary, Gastric acid Donepezil
Smooth Muscles Contraction = Miosis, Galantamine
Bronchospasm, Diarrhea, Urination Rivastigmine
Nicotinic Receptors: Indications

Nicotinic neural (Nn) Physostigmine - Glaucoma
Target Response Demecarium - GI and Urinary Tract Anatomy
Ganglion, CNS Stimulation Epi release Echothiophate
Edrophonium - - Myasthenia Gravis autoimmune disease
Nicotinic (Nm) Dx. (Tensilon (Progressive muscle, weakness, dropping of
Target Response Test) eyelids, Repiratory paralysis)
Neuromuscular endplates Skeletal muscle contraction = Pyridostigmine
Tremor Ambenonium
Neostigmine
Tacrine -
3. PARASYMPATHOMIMETICS Donepezil
Galantamine
Cholinergic Agonists Rivastigmine
Cholinomimetics
Mimicry Adverse Effects:
Diarrhea
Classifications: Urination
Miosis
Direct receptor
Direct-Acting activation Bradycardia, Bronchoconstriction
Emesis
Lacrimation
Indirect-Acting: Inhibit metabolism of Salivation, Sweating
Cholinesterase ACh Treatment:
Inhibitors
Primary:
Atropine
DIRECT-ACTING
Cholinesterase Reactivators
Choline esters
Pralidoxime
Non selective Acetylcholine Diacetylmonoxime
Carbachol
Metacholine
Muscarinic-selective Betanechol (Urecholine)

4. PARASYMPATHOLTICS Neuromuscular Blockers: Classifications
Depolarizing NMB Non-depolarizing NMB
Cholinergic Antagonists Succinylcholine Curare derivatives
Classifications - anti nicotinic agonist MOA: blocks Nm receptor

- Useful when rapid immediate paralysis
Antimuscarinics Muscarinic blocker endotracheal intubation is
required during the At low doses : competitively block
Antinicotinics Nicotinic blocker induction of anesthesia ACh at the nicotinic receptors,
- Used during preventing depolarization of the
electroconvulsive shock muscle cell membranes and inhibit
treatment muscle contraction
ANTIMUSCARINICS
MOA: irreversibly activates Nm At high doses : Blocks the ion
A.k.a. Anticholinergics receptor channels of the motor template,
Atropine leading to further weakening of the
Other Anticholinergics Phase of effect : neuromuscular transmission,
- Initial = skeletal muscle thereby reducing the ability of
Atropine contraction cholinesterase inhibitors to reverse
- Final = relaxation the actions of the nondepolarizing
Blocks M1: Inhibits gastric secretion paralysis blockers
Blocks M2: Tachycardia
Blocks M3: Inhibits secretion Adverse effect :
Dry mouth - Respiratory Paralysis: (Tx. Type I : Isoquinoline (-curium)
Anhidrosis Endrophonium, - Atracurium
Cutaneous vasodilation Neostigmine) - Tubocurarine
Erythema - Malignant Hyperthermia: Type II : Steroidal (-curonium)
(Tx. Dantrolene) - Pancuronium
Blocks M3: Smooth Muscles - Myalgia, Myositis, - Rocuronium
Mydriasis Rhabdomyolysis
Cycloplegia Adverse effects :
Bronchodilation - Respiratory/diaphragmatic
Ileus paralysis. (Tx :
Urinary retention Neostigmine,
CNS Effects Edrophonium)
- Tubocurarine
Acute Psychosis
anaphylactoid reaction
Confusion (Tx. Epinephrine)
Agitation
Disorientation DRUGS WITH IMPORTANT ACTIONS ON SMOOTH MUSCLE
Other Anticholinergics
CNS: Scopolamine, Trihexyphenidyl, Benztropine, Biperiden AUTACOIDS
Eyes Homatropine, Anistropine, Cyclopentolate
Bronchi Ipratropium, Tiotropium, Oxytropium
Localized hormones
Gastric Gland Pirenzepine, Telenzepine
GIT and Urinary Methscopolamine, Glycopyrrolate, Hyoscine,
Site of release = near the site of action
Bladder Dicycloverine, Oxybutinin, Scopolamine Produced by virtually all cells
Vs. Endocrine Hormones - Systemic; produced by
Clinical Uses specific cells
Atropine - Symptomatic Bradycardia
- Treatment of Cholinomimetic Poisoning Histamine
- Given with Diphenoxylate to minimize
addiction with Diphenoxylate
Serotonin
Scopolamine - Management of Motion sickness
Trihexyphenidyl - Management of EPS and Parkinsonism
Eicosanoids
Benztropine
Biperiden
Homatropine - Mydriatic Cycloplegics
Bradykinin
Anistropine
Cyclopentolate HISTAMINE
Ipratropium - Bronchial and COPD
Tiotropium
Oxytropium Locations:
Pirenzepine - Management of hyperacidity Mast cells
Telenzepine Basophils
Methscopolamine - Management of hypermotility D/O and Stomach
Glycopyrrolate urinary incontinence CNS
Hyoscine
Dicycloverine Biosynthesis
Oxybutinin
Scopolamine
ANTINICOTINICS
Muscle relaxant
Ganglionic Blockers
Neuromuscular Blockers
Ganglionic Blockers Neuromuscular Blockers Mechanism of Release:
are Nn blockers are Nm blockers
Skeletal muscle relaxants Ca2+ dependent
Hexamethonium - Used for spastic disorders degranulation
Trimethaphan - Anesthetic adjuncts
Mecamylamine
Ca2+ independent
- Vasodilation and Vesicle degranulation
anticholinergic
- These agents are no
Ca2+ dependent degranulation
longer clinically useful Induced by immunoglobulin E (IgE) fixation to mast cells
Anaphylaxis

Ca2+ independent degranulation Piperidine
Induced by drugs
Morphine Cyproheptadine
- also possesses antiserotonergic
Guanethedine
and anticholinergic activiies
Tubocurarine used in management of
Amine Antibiotics serotonin syndrome
Anaphylactoid reaction 2nd generation Piperazines
- Less lipohilic - Less sedating
Mechanism of Action - Less sedating
Binds histaminic receptors Cetirizine
Levocetirizine
HISTAMINIC RECEPTORS Piperidines
- True, non-sedating
Histaminic-1 (H1)
Vasodilation Loratadine
Bronchoconstriction
Pain and itchiness Desloratadine
Contraction of endothelial cells
Fexofenadine
Wakefulness
H2 antihistamines
Histaminic-2 (H2) - H2 blockers
Increase gastric acid production Cimetidine (least potent) - Promote healing of gastric and
Enhances degranulation of histamine Famotidine (most potent) duodenal ulcers
Histaminic-3 (H3) Ranitidine - Treatment of hypersecretory
Decrease histamine release Nizatidine states (Zollinger-Ellison
Histaminic-4 (H4) Syndrome)
Chemotaxis - Adjuncts in the management of
allergic reactions
Drugs
Cimetidine (prototype) - enzyme inhibitor
Agonists
Interactions = Toxicityanti-
Histamine No longer used clinically androgenic (gynecomastia, loss
Obsolete use : of libido, infertility)
- Pulmonary challenge test
- Test of gastric secretory function
Betahistine H1 agonist ; H3 antagonist
SEROTONIN
Use: Management of associated with Locations:

vertigo (Endolymph: presence of fluid in the inner ear) Enterochromaffin cells
Impromidine Investigational Platelets
Stomach
Antagonists CNS
Functional: Epinephrine
- Biosynthesis
-
Pharmacologic: Antihistamine
Antihistamine
H1 antihistamines
- anti-allergy
- Use: allergic reaction, asthma
- Do not give for bronchial asthma
1st generation (classical) Ethanolamines Mechanism of Action
- Lipophilic (can cross - most sedating Interacts with Serotonergic receptors
the Blood brain - most efficacious
barriers or BBB) SEROTONERGIC RECEPTORS
- Powerful central Diphenhydramine
anticholinergics - management of Acute Dystonic 5-HT1A
- Sedating agents Crisis
Decrease cAMP
Dimenhydrinate Pre-synaptic receptors (CNS)
Autoregulation
Carbinoxamine Inhibits further release of serotonin
5-HT1B/1D
Doxylamine Vascular smooth muscles
- Sleeping Aid Not involved: blood vessels in the heart and in the
Ethylenediamine skeletal muscles
Vasoconstriction
Tripelennamine
Pyrilamine 5-HT2
- Cause moderate sedation Enhances phospholipase C activity
Cause GI upset Smooth muscles (bronchi, blood vessels, intestines)
Piperazines contarction
Meclizine and
Cyclizine 5-HT3
- for motion sickness
Inotropic receptors
Hydroxyzine
prodrug; active form of Cetirizine 5-HT4
Alkylamines Enhances cAMP
Brompheniramine and
Chlorpheniramine component of OTC
cold medications
Phenothiazine
Promethazine
- preanesthetic agent

Drugs Platelets - Inhibits aggregation = PGE1
- Aggregation = TXA2
Agonists Eyes - Reduction of IOP = PGF
Buspirone - Partial 5-HT1A agonist enhances outflow of aqueous
- Anxiolytic humor
- Therapeutic effects: 2 weeks
-triptans: - 5-HT1B/1D Agonists Prostaglandin Analogs
Sumatriptan, - Inhibits vasodilation of cerebral blood vessels Misoprostol - PGE1 analog ytoprotectant
Naratriptan, - Inhibits inflammation of meninges - Treatment of NSAID-induced ulcer
Zolmitriptan - Use: Anti-migraine Agents - Abortifacient
- A/E: Increase in blood pressure Epoprostenol - PGI2 analog Vasodilation
Cisapride, - Management of irritable bowel syndrome with - Management of primary pulmonary
Tegaserod predominant constipation hypertension
(Partial 5-HT4 Dinoprostone - PGE2 analog Cervical opening
agonists) - Induction of abortion
Alprostadil - PGE1 analog Vasodilation
Prucalopride - Treatment of erectile dysfunction
(Full 5-HT4 Latanoprost - PGF analog Lowers IOP
agonist) - Treatment of glaucoma
Antagonists DRUGS THAT ACT IN THE CENTRAL NERVOUS SYSTEM

Cyproheptadine - Blocks 5-HT1 and 5-HT2 receptors
- Antihistaminic CENTRAL NERVOUS SYSTEM
- Anticholinergic
-setrons: - Block 5-HT3 receptors
Ondansetron - Prevention/ Treatment of chemotherapy-
consisting of the brain and spinal cord
Granisetron induced nausea and vomiting It is referred to a
Palonosetron the entire body and co-organs activity across the whole
organism
ERGOTS ALKALOID Brain control center of the body
Blood Brain Barrier a tightly packed layer of cells that line
Claviceps purpurea (Ergoline) the blood vessels in the brain & spinal cord
Strong structural similarity to DA, NE, and 5-HT Gatekeeping system that prevents entry of toxins and
only allowing entry of nutrients
Mehanism of Action In drugs, the BBB prevents entry of most drugs from the
Acts primarily on alpha-adrenergic receptorson uterine and blood
vascular smooth muscle, increasing uterine tone and causing Neuron
vasoconstriction
Drugs:
Also known as nerve cells, sends and receive signals

from the brain
EICOSANOIDS Soma carries genetic
and provides
From metabolism of 20-carbon, unsaturated fatty acids energy to drive activities
(eicosanoids acids) Axons allow neurons to send electrical signals to
Arachidonic acid other cells
Dendrites receives signals
Biosynthesis Nerve cells pass messages one to another and it is achieved
through chemical and electrical impulses
NEUROTRANSMITTERS
Phospholipids
Endogenous chemicals responsible for the transmission of signals
Phospholipase A2 Excitatory NT fires action potential
Inhibitory NT decrease the chances of neurons to fire
Arachidonic acid action potential
Cyclooxygenase Both Excitatory & Inhibitory NT: Acetylcholine,
Lipoxygenase
Norepinephrine, Serotonin, Glutamate
Leukotrienes Prostanoids Inhibitory NT: Dopamine, GABA, Glycine, Opioids
Actions GABA Gamma Amino Butyric Acid

Vascular smooth muscles - Vasodilation = PGE2, PGF , PGI2 Major inhibitory NT of the brain
(prostacyclin) Binds either GABAA or GABAB receptors
- Vasoconstriction = TXA2 GABAA receptor (ionotropic) opens Cl- channels
(thromboxane) GABAB receptor (metabotropic) opens K+ channels or
- Inflammation = PGI2 closes Ca2+channels
PGE2 , Inhibitory effects
LTB4
Fast Inhibitroy Postsynaptic Potentials (IPSPs) are blocked
Bronchi - Bronchodilation = PGE series
- Bronchoconstriction = PGF, LTC4, by GABAA receptor antagonists
LTD4 Slow-reacting Substances Slow IPSPs are blocked by GABAB receptor antagonists
of Anaphylaxis (SRSAs)
Uterus - Contraction of uterus and Glutamate
dysmenorrhea = PGE series, PGF Excitatory amino acid (EAA)
Stomach - Cytoprotection Stimulates EAA receptors (NMDAR & AMPAR)
pepsinogen secretion = PGE series
Thought to be important in learning, memory and other brain STATER PACK:
functions Reuptake inhibitors
Glutamine is imported to the glutamatergic neuron and Increase NT levels in the synapse
converted to glutamate by the enzyme glutamase MAO inhibitor
The glutamate is concentrated in the vesicular glutamate Increase NT levels in the synapse
transporter Receptor blocker
Upon release unto the synapse, the glutamate can interact to Decrease NT effects
Na channel blocker
its neurons in the post synaptic neuron such as NMDAR & Prevents depolarization causing inhibitory effect
AMPAR
Binding to its receptors (NMDAR & AMPAR) stimulates the
opening of Na & Ca2+ channels, causing cations influx PYSCHOSIS
producing depolarization in both synaptic neurons resulting
to excitatory effects Schizophrenia research suggests that a combination of
Some glutamate will enter the glutamate transporter and physical, genetic, psychological, environmental factors can
converted to glutamine by the enzyme glutamine synthetase make a person more likely to develop this condition
The glutamine will be transported in the pre-synaptic neuron have been reported to cause the
to be converted again as glutamate symptoms of schizophrenia
Schizophrenia is a type of disorder characterized by several
Dopamine types of symptoms, including:
An inhibitory NT due to activation of K+ channels or Positive symptoms
inactivation of Ca2+ channels Hallucinations (auditory: most common type)
D2 receptors is main subtype in the basal ganglia neurons Delusions (paranoia or grandeur delusions)
Disorganized speech (random rumbling of words)
Norepinephrine Bizzare behavior
Excitatory effects are produced by activation of 1 and 1 Negative symptoms
receptors Alogia (inability to speak because of mental defect,
Inhibitory effects are caused by activation of 2 & 2 mental confusion, or aphasia)
receptors Anhedonia (lack of interest pleasure)
Avolition (lack of motivation)
Serotonin Asociality (isolate themselves)
Serotonin can cause excitation or inhibition of CNS neurons Flattening of affect (poor eye contact
depending on the receptor subtype activated
Diagnosis
Targets of CNS drug action Person can be diagnosed at least one or two of the
symptoms
Types of Ion Channels: Experienced for 6 months in prodromal, active, or residual
phases
Voltage-gated ion channels respond to changes in Other causes of symptoms should be ruled out
membrane potential
Ligand-gated ion channels aka ionotropic receptors 1st generation/ Traditional/Classical/ Typical antipsychotics
MOA:
The Synapse & Synaptic potentials - Block D2 receptors (non-selective)
- reduction
of positive symptoms
Excitatory
-
Excitatory post-synaptic potential (EPSP) worsening of negative symptoms
Ionotropic receptor -
Extrapyramidal Symptoms
Inhibitory - Blockade of D2 receptors in
Inhibitory post-synaptic (IPSP) released
Presynaptic inhibition - Block HAM receptors (antiHistamine, anti-Alpha receptor, anti-
Muscarinic receptor)
Phenothiazines (-azine) Aliphatic (-promazine)
NEUROTRANSMISSION - Chlorpromazine
Piperazine (-phenazine)
Pre-synapse where the synthesis, storage, metabolism & - Fluphenazine
release occur Piperidine (-ridazine)
Synaptic cleft where most of the enzymes found - Thioridazine
Post-synaptic majority of the receptors located Butyrophenones (-peridol) Haloperidol
Droperidol
Sites of CNS drug action Thioxanthene (-thix) Thiothixene
Potency:
Drug may alter - Directly proportional with D2 receptors affinity

The action potential in the presynaptic fiber - Inversely proportional with HAM receptors affinity
Synthesis of transmitter
Storage 2nd generation/ Atypical antipsychotics
Metabolism MOA:
Release - Block D2 < D4 receptors
Reuptake - Block 5-HT2A receptors
Degradation -zapine Clozapine
Olanzapine
Receptors for the receptors
-xapine Loxapine
Receptor-induced decrease or increase in ionic -peridone Risperidone
conduction Paliperidone
Ziprasidone
How are NT terminated? Others Aripiprazole
Amisulpride
Diffuse and degrade Molindone
Quetiapine
Metabolism by COMT or MAO Advatange over Typical antipsychotics
Reuptake - Reduced side effect (espcially EPS)
- Greater affinity & activity in therapy-resistant schizophrenia
- More effective in treating negative symptoms

Efficacy: Therapeutic Uses of Antipsychotic Agents
- In treatment of positive symptoms: 1st gen = 2nd gen 1st Generation
- In treatment of negative symptoms: 2nd gen > 1st gen Chlorpromazine - Moderate to high potential for EPS
- Moderate to high potential for weight gain,
Clozapine orthostasis, sedation, antimuscarinic effects
- The only antipsychotic drug that DOES NOT cause EPS Fluphenazine - Oral formulation has a high potential for EPS
- Never given as a 1st line due to SAM (Seizure, Agranulocytosis, - Low potential for weight gain, sedation, and
Myocarditis) orthostasis
Other indications of antipsychotic drugs - Low to moderate potential for antimuscarinic
- Management of acute mania effects
- Management of severe depression - Common use is in the LAI formulation
- Management of phcyclidine intoxication (haloperidol) administered every 2 3 weeks in patients with
- Management schizophrenia and a history of noncompliance
with oral antipsychotic regimens
ADVERSE EFFECT OF ANTIPSYCHOTIC DRUGS Haloperidol - High potential for EPS
- Low potential for anti-adrenergic (orthostasis)
a. Due to Dopamine receptor blockade or antimuscarinic adverse events, weight gain
or sedation
2nd Generation
Extrapyramidal syndrome (EPS)
Aripiprazole - Low potential for EPS; low potential for weight
A movement disorder because of Dopamine and gain; low potential for sedation and
Acetylcholine imbalance antimuscarinic effects
- management: decrease Acetylcholine - Approved for the treatment of bipolar disorder
- Anticholinergics (centrally acting): Biperiden, Benztropine, - Also approved for autistic disorder in children,
Trihexyphenidyl - An adjunctive treatment for major depression
Akathisia Clozapine - Very low potential for EPS; risk for blood
Uncontrolled restlessness dyscrasias. Risk for seizures; risk for
myocarditis
Most difficult to treat EPS - High potential for the following: sialorrhea,
Only EPS not treated by Anticholinergic drugs weight gain, antimuscarinic effects,
orthostasis, and sedation
Dystonia Olanzapine - Low potential for EPS
Usually the 1st EPS seen - Moderate to high potential for weight gain and
Torticollis/Retrocollis (twisting of the neck) sedation
Easier to treat but FATAL - Low potential for orthostasis;
- Approved for the treatment of bipolar disorder
Management : IV diphenhydramine, Anticholinergic
Paliperidone - Low to moderate potential for EPS
agents - Low potential for sedation and weight gain
Pseudo parkinsonism (low DA levels) Quetiapine - Low potential for EPS
Tremors, rigidity, akinesia, postural instability - Moderate potential for weight gain, orthostasis
Tardive dyskinesia - Moderate to high potential for sedation
Potentially irreversible - Approved for the treatment of bipolar disorder
Due to: hypersensitivity of D2 receptor and as an adjunctive treatment for major
Characterized by: Tic-like motion depression
Risperidone - Low to moderate potential for EPS, weight
Management: discontinue drug, use Clozapine/
gain, orthostasis; sedation
Olanzapine - Also approved for the treatment of bipolar
disorder
Hyperprolactinemia - Also approved for autistic disorder in children
Promotes lactation Ziprasidone - Low potential for extrapyramidal effects
Dopamine = prolactin- - Contraindicated in patients with history of
Amenorrhea, galactorrhea, impotence cardiac arrhythmias
Bromocriptine (D2 agonist) given to mothers who wish to - Minimal weight gain
- Used in treatment of bipolar depression
stop breast-feeding
Neuroleptic malignant syndrome (NMS) MOOD DISORDERS

Malignant hyperthermia
Management :
- Dantrolene (Ca+ antagonist; muscle relaxant) emotional state
- Bromocriptine (D2 agonist) It is a disorder characterized by long period of extreme
happiness, extreme loneliness, or both
b. Due to Histamine receptor blockade Mood regulation: 5-HT, Dopamine, NE
Sedation - 0 +
c. Due to Alpha 1 receptor blockade Major Mild Normal Mild mania Mania
Orthostatic hypotension depression depression (Hypomania)
(Dysthymia)
d. Due to Muscarinic blockade
Anticholinergic Mixed Disorders:
Bipolar disorder: Mania and Major depression
Other adverse effects: Cyclothymia: Dysthemia and Hypomania
Seizure: Clozapine (most common)
Agranulocytosis: Clozapine; require WBC count monitoring Bipolar Disorder
every week for the 1st 6 months of therapy and every 3 Formerly known as manic-depressive illness or manic
weeks thereafter depression
Cardiac side effect: Myositis (Clozapine ); QT prolongation A mental disorder that causes unusual shifts in mood
(Mioridazine, Ziprasidone, Thioridazine); Myocarditis
(Clozapine) The Diagnostic & Statistical Manual of Mental Disorders
Classification of Bipolar Disorder
Bipolar I disorder At least one manic episode, which may have
Retinal deposit (causes blindness): Thioridazine been preceded by and may be followed by
Weight gain: common to 2nd gen antipsychotics; except hypomanic or major depressive episodes
Amisulpride, Molindone, Aripiprazole Bipolar II disorder At least one hypomanic episode and a current or
Risk of Diabetes Mellitus : Olanzapine past major depressive episode
Cyclothymic Disorder Defined by periods of hypomanic symptoms
(Cyclothymia) as well as periods of depressive symptoms
lasting for at least 2 years

Clinical Presentation of Bipolar Disorder Drugs that - Thiazide diuretics
increase the - ACE inhibitors
serum - Na Loss
Major Depressive Episode concentration of - NSAIDs
Delusions, hallucinations and suicide attempts are more Li
common in bipolar depression than in unipolar depression Adverse Effects - GI distress such as nausea, vomiting and
diarrhea
Manic Episodes - Vasopressin deficiency (polyuria,
Acute mania usually begins abruptly, and symptoms polyphagia)
increase over several days. Bizarre behavior, - Fine hand tremor
- Muscle weakness (transient)
hallucinations,and paranoid or grandiose delusions may - Nephrogenic DI (low sp.gr. of urine)
occur. There is marked impairment is functioning. excretion of water making the urine diluted
Manic episodes may be precipitated by stressors, sleep - Goiter and/or hypothyroidism
deprivation, antidepressants, central nervous system Toxicites serum levels greater than 1.5 mEQ/L (mmol/L)
- Coarse tremors, ataxia, confusion, slurred
Hypomanic Episodes speech and seizure
There is no marked impairment in social or occupational - Combination with typical antipsychotics,
verapamil or diltiazem is reported to cause
functioning, no delusions, and no hallucinations. Some
neurotoxicity
patients may be more productive than usual, but 5% to 15% Valproic Acid
of patients may rapidly switch to a manic episode Divalproex Equal effectiveness with lithium for pure mania
sodium (sodium Better than Li in treating rapid cycling
Pharmacologic Treatment of Bipolar Disorder valproate)
Adverse Effects: (dose-related)
Lithium, Divalproex sodium (valproate), Extended-release - GI complaints
- Fine tremors
Carbamazepine, Aripiprazole, Azepine, Olanzapine, - Sedation
Quetiapine, Risperidone, and Ziprasidone are currently Carbamazepine, Lamotrigine
approved by the FDA for treatment of acute mania - Can be used as prophylaxis and treatment of mania
Lithium, Divalproex sodium, Aripiprazole, Olanzapine, and - For acute and maintenance therapy
Lamotrigine are approved for treatment Antipsychotics
Aripiprazole, are effective as monotherapy or add-on therapy to
CANMAT Guidelines for Long-term Treatment of Bipolar Disorder Azepine, lithium or valproate for acute mania
1st line 2nd line 3rd line Haloperidol,
- Lithium - Carbamazepine - Adjunctive Olanzapine,
- Lamotrigine - Lithium + Phenytoin Quetiapine,
monotherapy Divalproex - Adjunctive Risperidone,
(limited efficacy - Lithium + Clozapine
Ziprasidone
in preventing Carbamazepine - Adjunctive ECT
mania) - Lithium or - Adjunctive Alternative treatments
- Divalproex Divalproex + Topiramate - High potency BZD (Clonazepam, Lorazepam)
- Olanzapine Olanzapine - Adjunctive - Antidepressants (Note: monotherapy with antidepressants can
- Quetiapine - Lithium + omega -3- fatty precipitate mania in bipolar patients)
- Lithium or risperidone acids
Divalproex + - Lithium + - Adjunctive
Quetiapine Lamotrigine - Oxcarbazepine, DEPRESSION
- Risperidone - Olanzapine + - Adjunctive
- Adjunct Fluoxetine - Fabapentin
Risperidone LAI Major Depressive Disorder (unipolar)
- Aripiprazole A depression of mood without any obvious medical or
(mainly for situational causes, manifested by an inability to cope w/
preventing
mania)
ordinary events or experience pleasure
- Adjunctive The essential feature of MDD is a clinical course
Ziprasidone characterized by one or more major depressive episodes
without a history of manic or hypomanic episodes
Note:
Not Recommended: Adjunctive flupentixol, monotherapy with MONOAMINE HYPOTHESIS OF DEPRESSION
Gabapentin, Topiramate or Antidepressants
Lithium DOC for euphoric mania

Low
Divalproex has better efficacy for mixed states, dysphoric mania NE
and rapid recycling
Antimania
Lithium carbonate
Depression
MOA -
recycling Low
- Inhibits the Low
5-HT DOPA
- Inhibition of dopamine neurotransmission
Dopamine is known to be elevated in NE and 5-HT neurotransmission
mania and decrease in depression
- Inhibition of glutamate neurotransmission
Glutamate is an excitatory NT and can NE: binds to its receptor
lead to excitotoxicity in increase levels NE reuptake via NRT
- Increasing & activating GABA Metabolites (degraded by MAO)
neurotransmission
GABA is an inhibitory NT that plays a role 5-HT: binds to its receptor in the post-synaptic neuron
in modulating glutamate and dopamine 5-HT reuptake via SERT
In bipolar affective d/o = diminished GABA
degraded by MAO
neurotransmission = excitatory toxicity
Uses - 1st line agent for acute mania, acute bipolar
depression Antidepressants
- Maintenance tx of bipolar I or II disorders Effects: increase levels of NE, 5-HT anddopamine
Limitation - Not as effective in treating rapid cycling Tricyclic MOA :
- Has narrow TI antidepressant - block reuptake of Norepinephrine and
Drugs that can - Xanthine diuretics Serotonin ( NE > 5-HT )
lower the serum - Osmotic diuretics - other blocking activity: anti- HAM
concentration of - Na supplementation (antiHistamine , Alpha receptor blockers, Anti
Li - Acetazolamide Muscarinic receptors)

Examples: Types of Anxiety Disorder
- Amitriptyline, Nortriptyline -triptyline
- Imipramine Desipramine - -pramine
- Doxepin, Clomipramine Generalized anxiety disorder (GAD)
Persistent or excessive worrying(at least 6 months)
Uses: Worrying about schoolworks or performance
- Management of neuropathic pain (Amitriptyline) Restless
- Drug of choice of enuresis or bed wetting Difficulty in concentrating (mind going blank)
(Imipramine) Irritable
- Management of insomnia and anxiety disorder
Muscle tension
Adverse effects : Having sleep problems
- Weight gain, QT prolongation, sedation,
orthostatic hypotension Panic disorder
Tetracyclic Examples: Recurrent unexpected panic attack or persistent worrying for
antidepressant - Mianserin having panic attack
- Amoxapine Panic attack is abrupt surges of intense fear or
- Maprotiline extreme discomfort w/c reach a peak within minutes
MAO inhibitors MOA: inhibit both MAOA and MAOB
Cognitive Symptoms
MAOA metabolizes NE, 5-HT, tyramine, histamine
MAOB metabolizes dopamine Palpitations
Sweating
Non-selective MAO inhibitor Shortness of breath
- Phenelzine Fear of going crazy or fear of dying
- Isocarboxazid
- Tranylcypromine Obsessive Complusive Disorder (OCD)
Selective MAOA Inhibitor
Obsessions has certain thoughts repeatedly
- Moclobemide
Selective MAOB Inhibitor Compulsions perform certain routines repeatedly
- Selegiline Obsession of germs compulsion: keeps washing his hands
repeatedly
Use: Management of atypical depression (psychotic Obsession of intruders compulsion: checking the doors if it
features; phobia) was locked several times
Drug interactions :Tyramine-rich food (cheese, wine,
Post-traumatic disorders (PTSD)
beer, chicken, liver, banana) will cause hypertensive
crisis Classified under the category of trauma and stress related
disorder
Adverse Effects: Orthostatic hypotension,anticholinergic
effects, weight gain Social Phobia
Intense anxiety or fear of being judge negatively evaluated or
Toxicity: shock, hyperthermia, seizure, serotonin rejected in a social or a performance situation
syndrome
Atypical Nefazodone
antidepressant Trazodone
Separation anxiety Disorder (SAD)
- MOA: blocks 5-HT reuptake An individual or child experiences excessive anxiety
- Adverse effect: sedation regarding separation from home or to an individual who has
- Use: hypnotic drugs; off label management of strong emotional attachment
insomnia
- Adverse effect: priapism or prolonged erection Selective mutism
NE-Dopamine Bupropion Complex childhood anxiety disorder characterized inability to
reuptake Use: smoking cessation
speak and communicate effectively in selected social setting
inhibitor
such as school
They able to speak in social setting where they feel
Special Populations
comfortable, relax, and secured
Elderly Patients
Agoraphobia
Depressed mood may be less prominent than other
Fear of being in situation where escape might be difficult or
symptoms
SSRI are often considered as 1st choice
Bupropion, Venlafaxine and Mirtazapine are also effective
Anxiety Disorder due to another medical condition
and well tolerated
Pedriatric Patients
NEUROTRANSMISSION AND ANXIETY
Symptoms of depression in childhood include, boredom,
anxiety, failing adjustment, & sleep disturbances
Mediators of Anxiety:
Data supporting efficacy of antidepressants in children 7
NE
adolescents are sparse
5-HT
Fluoxetine is the only FDA approved antidepressant for
Dopamine
treating depression in px below 18 years of age
GABA
Amygdala section of the involved in learning about fear,
ANXIETY
danger, and safety
Too much excitatory effects in the amygdala
Most common type of psychiatric disorder American
Normally the GABA controls the activities of amygdala by
Psychiatric association
activating the inhibitory neuron and stop the neuron from
sending to another neuron
Normal anxiety Pathological anxiety
Common; in response to a threat No real source of fear or excess of
provoking fear GABA and MOA of Agents
Temporary; short duration Chronic; recurrent course
Situational Multiple symptoms affecting daily GABA major inhibitory NT in the CNS
life Pentameric in form because it has 5 subunits
Example: Example: 2 alpha sub-unit
Nervousness about public speaking Nervousness about going out to the 2 beta sub-unit
public 1 gamma sub-unit
Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) 2 types of receptors:
GABAA receptor ionotropic
physical symptoms cause clinically significant distress or impairment in social,
occupational, or other important ar GABAB receptor metabotropic

Binding of GABA in the GABAA receptor(ligand-gated)
stimulates the opening of Cl-channels promoting Cl-influx. Non-benzodiazepines
Entry of Cl-ions results to Hyperpolarization of the post- Eszopiclone - subunit of GABAA
synaptic neuron to generate a post-synaptic potential Zolpidem receptor
producing inhibitory effects Zaleplon - Sedative
Benzodiazepines -zepam; -zolam

anticonvulsant
MOA - Act on a receptor located between alpha
and gamma subunits
Ramelteon
- Stimulates binding of GABA on GABAA
receptors - novel hypnotic drug; no direct effects on GABA
- Increase the frequency of opening the Cl- - activates melatonin receptors
channels - decreases latency of sleep onset with minimal rebound
Short acting Midazolam insomnia or withdrawal symptoms
Triazolam - less likely to be abused; not a controlled substance
Intermediate acting Lorazepam
Temazepam
Oxazepam Buspirone
Alprazolam - partial agonist of 5-HT1A receptors
Flunitrazepam - sedative anxiolytic with minimal CNS depressants effects
Clonazepam - No significant interaction with other sedative hypnotics
Long acting Diazepam - no muscle relaxation
Clorazepate - no analgesia
Chlordiazepoxide
- no dependence
Metabolism Benzodiazepine Phase I (CYP3A4)
metabolites Phase - no euphoria
- no potential for abuse
Drugs with Active Nordiazepam
metabolites Oxazepam Clinical Effects; Sedative-hypnotics
Drugs without Clonazepam
Active metabolites Oxazepam
Lorazepam
CNS depression dose dependent
Alprazolam Tranquilizing
Effects of BZDs on - Stage 1: the latency of sleep onset is Sedation
sleep pattern decreased (time to fall asleep) Hypnosis
- Stage 2: the duration of stage 2 NREM Anesthesia
(nonrapid eye movement) sleep is inc Respiratory depression
- The duration of REM sleep is decreased Coma
- The duration of stage 4 NREM slow-wave
Death
sleep is decreased
Anterograde amnesia
Barbiturates
Transient loss of memory after administration of high doses
Ultra-short acting Thiopental
Thiamylal of BZDs
Methohexital Basis for date-
Acceptable use: during surgery
- Rapid onset: acts within seconds - Anesthesia can be produced by most barbiturates (e.g.,
- Short DOA: 30 mins thiopental) and certain benzodiazepines (e.g. midazolam)
- Use: induction of anesthesia
- Very high lipophilicity
Anticonvulsant
- Plasma binding: high (>70%)
Short-acting Pentobarbital
Clonazepam, nitrazepam, lorazepam and diazepam
Hexobarbital selected management for seizures)
Secobarbital Phenobarbital & metharbital (alt for generalized tonic-clonic
seizure; has been regarded as DOC for febrile seizure
- Use: Sedatives for insomnia
- Relatively rapid onset: 10-15 mins Muscle relaxation
- Relatvely short DOA: 3-4 hours Occurs only w/ high doses of most sedative hypnotics
- High lipophilicity
- Plasma binding: high (70%)
Diazepam is effective at sedative dose levels for specific
Intermediate-acting Amobarbital spasticity state including cerebral palsy
Butobarbital High doses of most of the barbiturates and some of the
BZDs
- Use: Hypnotics
- Relatively slow onset: 45-60 mins Enzyme induction
- Intermediate DOA:6-8 hours Phenobarbital
- Intermediate lipophilicity
- Containdicated in patients with intermittent porphyria
- Plasma binding: intermediate (50%)
Long-acting Phenobarbital
Metharbital Tolerance & dependence
Mephobarbital Tolerance a decrease in responsiveness whichoccurs
when sedative hypnotics are used chronically or in high
- Relative slow onset: 30-60 mins dosage Cross-tolerance: develop tolerance in a sedative-
- Relatively long DOA: 10-16 hours hypnotic drug and develop tolerance in another sedative
- Use: Pain/ Migraine relief hypnotic drug
- Relatively low liphophilicity
- Plasma binding: low (<40%)
MOA of tolerance (BZD): down-regulation of BZD receptors
- MOA: Dependence an altered physiologic state that requires
Act on a receptor located between alpha continuous drug administration to prevent an abstinence or
and beta subunits withdrawal syndrome-psychological dependence and
Stimulates binding GABA on physiological dependence
GABAAreceptors Withdrawal signs: anxiety, tremors, hyperreflexia, and
Increase the duration of opening the Cl- seizures, occur more commonly
channels
- Blocked AMPAR
long acting = less likely to cause withdrawal signs
- can bind directly on the receptors short acting agent (e.g., triazolam) = daytime anxiety
- more potent zolpidem, zaleplon, & eszopiclone withdrawal
- higher toxicity symptoms are minimal after their abrupt discontinuance
- narrow TI
- more pronounced central depressant effect
Clinical Uses A partial seizure preceded to a generalized tonic-clonic
seizure
1. Management of anxiety states
Generalized seizure both hemisphere
2. Management of sleep disorders/ insomnia Grand mal seizure
Lower doses should be used in elderly patients Body becomes entire rigid
Zolpidem, Zaleplon, and Eszopiclone have rapid onset with Uncontrolled jerking
minimal effects on sleep patterns and cause less daytime Absence seizure (petit mal)
cognitive impairment than benzodiazepines Common in children
Blank stares
3. Management of seizures Lip smacking
Clonazepam, Diazepam, Phenobarbital Short DOA (less than 15 secs)
Atonic seizure
4. Induction of anesthesia Myoclonic seizures
Short-acting agents: Thiopental, Midazolam Sudden twitches of arm or legs
5. Management of bipolar disorder Status epilepticus

Clonazepam Recurrent seizure without regaining consciousness
Seizure last at least 30 minutes
6. Management of withdrawal states (ethanol and other sedative-
hypnotics) Acute seizure
Diazepam, Chlordiazepoxide, Phenobarbital (less likely)
Drugs for Seizure
7. For muscle relaxation in specific neuromuscular disorders Partial Seizure
Meprobamate, benzodiazepines Drug of choice Phenytoin
Carbamazepine
Alternative Lamotrigine
8. Management of neonatal hyperbilirubinemia Oxcarbamazepine
Phenobarbital Valproic acid
Generalized Siezure/ Grand-mal
9. As diagnostic aids or for treatment in psychiatry Drug of choice Valproic acid
Alternative Topiramate
Toxicity Lamotrigine
Additive CNS depression Absence Seizure/ Petit-mal
Overdosage Drug of choice Ethosuximide
Overdosage of sedative hypnotic drugs causes Alternative Valproic acid
severe respi and CVS depression Acute Seizure
Drug of choice Diazepam
More common with barbiturates than BZDs and newer
Atonic Seizure
agents Drug of choice Clonazepam
Management of intoxication: Alternative Valproic acid
flumazenil for BZDs, eszopiclone, zolpidem and Topiramate
zaleplon Lamotrigine
Urinary alkalinization for phenobarbital and other Status Epilepticus
barbiturates Drug of choice Lorazepam
ADR Old drug of choice Diazepam
Relatively low doses may lead to drowsiness, impaired
judgment, and diminished motor skills, sometimes with a Carbamazepine - Na channel blocker
- Enzyme inducer; Auto inducer (can induce
significant impact on driving ability, job performance, and
its own metabolism)
personal relationships. - Common dose-related adverse effects:
Elderly patients are more likely to experience thetoxicity so diplopia (double vision), ataxia (loss of
the dose should be adjusted involuntary control)
Reports of teratogenicity leading to fetal deformation - DOC for trigeminal neuralgia; neuropathic
BZDs are classified as either FDA pregnancy category pain
D or X Phenytoin/ - MOA: inhibits Na, K, Ca conductance
Diphenylhydantoin - Enzyme inducer
- Adverse effects: Nystagmus
SEIZURES
Valproic acid - Broadest spectrum
- Enzyme inhibitor
Epilepsy is a neurological disorder in which brain activity - MOA: increase GABA concentration;
becomes abnormal causing seizures or period of unusual stimulate glutamic acid decarboxylase
behavior sensations, sometimes loss of awareness enzyme needed for GABA synthesis
Define by the occurrence of at least 2 unprovoked - Adverse effects: hepatotoxic, teratogenic
seizures separated by at least 24 hours (neural tube defect or spina bifida)
During an epileptic seizure, neurons are firing electrical Lamotrigine - Na and Ca channel blocker
Ethosuximide - Reduces propagation of abnormal electrical
impulses all at thesame time, almost like an electrical storm
activity in the brain, most likely inhibiting T-
type calcium channels
Goal: decrease excitatory activity or increase inhibitory Topiramate - Na and Ca channel blocker
activity
First aid for Seizures
Type of Seizure Cushion head, remove glasses
Loosen tight clothing
Focal Seizure only one hemisphere Turn on side
Simple Focal Seizure Time the seizure w/ watch
Aka Jacksonian seizure remains conscious
Change the emotions or senses Look for I.D
Involuntary jerking
Complex focal seizure As seizure ends
Aka psychomotor seizure Offer help (as soon as the seizure end)
Loss consciousness
Hand rubbing, chewing/ swallowing, walking in circles
Secondary generalized seizure

PARKINSONISM L-AAD inhibitor Carbidopa, Benserazide
-
Disorder of the middle-aged or elderly people - reduces the metabolism of levodopa in the
periphery only
Neurodegenerative disorder along with
- Intial dose: L-dopa 300 mg/day (in divided
multiple sclerosis and amyotrophic lateral sclerosis caused doses) combined w/ carbidopa
by slowly dying neurons - Maximal dose: L-dopa 800-1000 mg/day
Substantia nigra with carbidopa 75mg or higher
chemical messengers to transmit signals between 2 regions COMT Entacapone, Tolcapone
of the brain to coordinate activity inhibitors - inhibits the COMT in the periphery and the
brain
causing decrease of dopamine production MAOB Selegiline, Rasagiline
inhibitors - inhibits MAOB in the brain
Imbalance between dopamine and acetylcholine Advantage:
Manifestations (TRAPS) - Extend the duration of Levodopa up to 1 hour
Tremors - Reduce the dose of L-dopa by as much as ½
Rigidity Adverse effects:
Akinesia - Inc peak effects of Levodopa
Postural instability - Worsen pre-existing dyskinesia or psychiatric
Shuffling gait symptoms such as delusions
Metabolites of selegiline:
- L-methamphetamine
The Hoehn & Yahr Scale is the most commonly used scale to - L-amphetamine
patients in Oral disintegrating tablet is preferred for improved
the following response and fewer side effects
Stage 1 Unilateral involvement only Amantadine - Antiviral
Stage 1.5 Unilateral and axial involvement - Releaser of dopamine
Stage 2 Bilateral symptoms, no impairment of balance - Dopamine reuptake inhibitor
Stage 2.5 Mild bilateral disease with recovery on pull test - ACh receptor blocker
Stage 3 Mild to moderate disease physically independent - NMDA receptor blocker
Stage 4 Severe disability, still able to walk or stand unassisted Adverse effects:
Stage 5 Wheelchair-bound or bedridden unless assisted - Sedation
- Dry mouth
Non-motor symptoms - Hallucination
- Dizziness
Impaired sense of smell, sleep disorders, cognitive - Confusion
symptoms, constipation, bladder symptoms, sweating, - Livedo reticularis
sexual dysfunction, fatigue, pain (particularly in a limb), Caution:
tingling, lightheadedness - doses should be reduced in patients with renal
dysfunction and those on hemodialysis
Dopamine Ergot derivatives
(D2) receptor - Bromocriptine
agonist - Cabergoline
Treatment options:
- Pergolide
Surgery Non ergot derivatives
Medications - Ropinirole
Temporary relief from the symptoms - Pramipexole
Do not reverse the neurodegeneration Safer and effective as monotherapy in mild to moderate
PD & as adjunct to L-dopa in patients with motor
Goal: ACh = Dopamine fluctuations
- Preferred for younger patients
Increase levels of dopamine
- Not preferred for older px (developed
Decrease levels of acetylcholine psychosis and orthostatic hypotension)
Anticholinergic Biperiden, Benztropine, Trihexyphenidyl
Drugs for Parkinsonism agents - Can be used as monotherapy or in conjunction
Levodopa - Immediate precursor of dopamine (centrally- with other antiparkinson drugs
- With the aid of amino acid transporter, the acting) Adverse effect: Alice in the Wonderland effect
levodopa can pass through the BBB
- Inside the brain the levodopa can now ANESTHESIA
beconverted to dopamine by the enzyme
amino acid decarboxylase
- In the periphery, the levodopa encounters AAD Loss of sensation with or without loss of consciousness
can result to initial conversion of levodopa to Classified as
dopamine. If this happens, levodopa General anesthesia a state characterized by
effectiveness is reduced as the dopamine unconsciousness, analgesia, amnesia, skeletal muscle
cannot enter the brain relaxation, and loss of reflexes
- The free levodopa can also encounter COMT Inhaled anesthesia
enzyme in the periphery which will be
Intravenous anesthesia
degraded into its inactive form
- The inactive metabolites of levodopa can no Local anesthesia refers to loss of sensation in a limited
longer be recognized by amino acid transporter region of the body
thus it can no longer enter the brain
- Into the brain, the dopamine can be degraded Stages and Depth of Anesthesia
by MAOB and COMT into its inactive form Stage 1: Analgesia Patient has decreased awareness of pain
Homovanillic acid sometimes with amnesia; consciousness may be
Use: impaired but not lost
- Due to delayed GER or decrease absorption Stage 2: Excitatory Patient is delirious and excited; Amnesia occurs,
- reflexes are enhanced, and respiration is typically
Management: irregular; retching and incontinence may occur
- Crush L-dopa/carbidopa tablets and take with a Stage 3: Surgical Patient is unconscious and has no pain reflexes;
glass of water or respiration is very regular, and BP is maintained
- Use orally disintegrating tablet on an empty Stage 4: Medullary Patient develops severe respiratory and CVS
stomach Depression depression that requires mechanical and
- Rescue drug: Apomorphine SC pharmacologic support
Due to long-term use -of-
and peak-
Management: Induction
- Bedtime administration of D2 agonist or The time from administration of a potent anesthetic to
- Sustained release development of effective anesthesia
Due to peak striatal dopamine levels dyskinesia
Due to initial conversion into dopamine in the periphery
N&V, cardiac arrhythmias, hypotension
Maintenance Barbiturates - Thiopental, Methohexital
Provides sustained anesthesia - Replaced by propofol
BZDs - Commonly used in the perioperative period
include midazolam, lorazepam, and less
Recovery
frequently diazepam
Time from discontinuation of anesthetic until consciousness - Produce minimal depression of ventilation,
and protective reflexes return although transient apnea may follow rapid
IV administration of Midazolam for
Anesthesia Protocols induction of anesthesia
Etomidate - GABA-mimetic
- An IV anesthetic with hypnotic but not
For minor procedures
analgesic effects and is often chosen for
Conscious sedation techniques (IV agents with local its minimal hemodynamic effects
anesthetics) Ketamine - NMDA receptor inhibitor
For more extensive surgical procedures - Partially water-soluble; highly lipid-soluble
IV drugs to induce the anesthetic state, inhaled anesthetics phencyclidine derivative
(with or without IV agents) to maintain an anesthetic state, - Produces significant analgesia
and neuromuscular blocking agents to effect muscle - cataleptic state
relaxation - S(+) form is more potent than R (-) isomer
Dexmedetimidine - -adrenegic agonist
Assessment of depth of anesthesia during surgery
- Principally used for the short-term sedation
Vital sign monitoring of intubated & ventilated
Cerebral monitoring (EEG) Opioid Analgesics - Strong opioids (morphine, fentanyl,
sulfentanyl)
Mechanism of Action in General Anesthetics - Analgesic agents and are distinct from
Anesthetics = CNS depressant general anesthetics and hypnotics
Increase inhibitory (GABA) synaptic activity - Routinely used to achieve postoperative
Inhaled anesthetics, Barbiturates, BZDs, Etomidate, analgesia and intraoperatively as part of a
balanced anesthesia regimen
and Propofol
Decrease excitatory (glutamate or ACh) synaptic activity
Local Anesthetics
Inhaled anesthetics (Nicotinic receptor antagonists)
Ester Type: 1i - Cocaine
Ketamine (NMDA receptor antagonist) - Procaine
- Chloroprocaine
Inhaled Anesthetics Amide Type: 2i - Lidocaine
Nitrous Oxide - Non-volatile gas - Bupivacaine
- Weakest anesthetic; potent analgesic - Prilocaine
Desflurane - Popular anesthetic for out-patient
procedures MOA: blockade of voltage-gated sodium channels
Sevoflurane - AOC: children (less pungent)
Isoflurane
Factors that determine systemic absorption of local anesthetics:
Enflurane - AOC: for asthmatic patient
Halothane - AOC: children (less pungent)
Dosage
- Most hepatotoxic Site of injection
Methoxyflurane - Potent anesthetic; weakest analgesic Drug-tissue binding
- AOC: during labor Local tissue blood flow
The rest is volatile liquids Use of a vasoconstrictor (e.g. epinephrine)
- downward direction (N to M): increasing potency Physicochemical properties
- upward direction (M to N): increasing MAC
Note: MAC is the median effective dose (ED50) of the anesthetic, Toxicities:
expressed as the percentage of gas in a mixture required to achieve that
effect
Systemic toxicity
Toxicities: CNS toxicity
Acute Toxicity sedation, light-headedness, visual and auditory
- Nephrotoxicity disturbances and restlessness
metabolism of enflurane and sevoflurane may generate Cardiotoxicity
compounds that are potentially nephrotoxic Bupivacaine most cardiotoxic
enflurane with prolonged exposure significant renal injury Local toxicity
- Hematoxicity
nitrous oxide megaloblastic anemia
Neural injury
- Hepatotoxicity local anesthetic agents were potentially neurotoxic
Halothane hepatitis durocaine a spinal anesthetic formulation
- Malignant hyperthermia containing procaine
important cause of anesthetic morbidity and mortality Transient Neurologic Symptoms (TNS)
Chronic Toxicity Syndrome of transient pain or dysesthesia has
- Mutagenicity, teratogenicity, carcinogenicity been linked to use of lidocaine for spinal
anesthesia
Intravenous Anesthetics
Propofol - Most frequently administered for induction DRUGS USED TO TREAT DISEASES OF THE BLOOD,
of anesthesia
INFLAMMATION, & GOUT
- Also used for maintenance of anesthesia
(continuous infusions)
- Milky white appearance; slightly viscous; COAGULATION DISORDER
pH ~7
- Formulated as an emulsion containing: Hemostasis
10% soybean oil Balance
2.25% glycerol Vascular event: vasoconstriction
1.2% lecithin
Cellular event: platelet migration and aggregation
susceptible px may experience allergic
reactions Protein event: coagulation factor cascade
- Act as hypnotic but does not have
analgesic properties Stimuli
- Has antiemetic action Endothelial injury
Fospropofol - A water-soluble prodrug of propofol Presence of Foreign bodies
rapidly metabolized by alkaline Stasis of blood
phosphatase, producing propofol, Arterial clots: platelet-
phosphate, and formaldehyde
- Licensed by the FDA in 2008 as a sedating
Venous clots: fibrin-
agent for use in adult patients during
monitored anesthesia care Coagulation Cascade

- Given as IV infusion for post
angioplasty to prevent acute
thrombosis
Adenosine and Dipyridamole
Phosphodiesterase - MOA: inhibits adenosine uptake,
inhibitor CGMP phosphodiesterase and
CAMP phosphodiesterase
- Use: Primary and Secondary
prevention of acute myocardial
infarction (only effective if given with
other antiplatelet or anticoagulant
drugs)
-
phenomenon
Cilostazol
- Effect: vasodilator
- Use: intermittent claudication
Anticoagulant
Direct thrombin inhibitor MOA:
- Interfere the coagulation cascade
- Inactivate of inhibit factor II-a directly
Parenteral
Hirudin
Intrinsic pathway: XII, XI, IX, X - natural product from Leeches
Extrinsic Pathway: III, VII X Lepirudin
- recombinant form; clinically used;
DOC for HIT or Heparin induced
Dissolution thrombocytopenia
Bivalirudin
- small molecule that inactivates factor
II-a; used as a antithrombotic post
angioplasty
Argatroban
- alternative in the management of HIT
Oral
Dabigatran
- Oral factor II-a inhibitor
- Prophylaxis against VTE
- Substitute or Alternative for warfarin
- Adverse effects: bleeding
- Drug interaction: CYP3A4 inhibitor
Indirect Thrombin MOA: inhibits factor synthesis or formation of
inhibitors active clotting factors (factor II-a)
Parenteral
Heparin
- Sulfated mucopolysaccharide;
released by platelets
Anti-thrombotics - 2 forms:
Anti-platelet Aggregants - High molecular heparin/ Regular/
Thromboxane synthesis Aspirin Unfractionated
inhibitor - Low molecular heparin/ Fractionated
MOA: Heparin
- inhibits COX of platelets, therefore Regular/ HMWH/ Unfractionated Heparin
decreasing levels of TXA2; (UFH)
Irreversibly acetylates COX of - MOA : binds and forms an active
platelets complex with anti thrombin or anti
- For primary and secondary thrombin III
prevention of acute myocardial - Monitoring parameters : aPTT / PTT
infarction LMWH/ Fractionated Heparin and Analogues
- Secondary prevention of stroke - MOA : forms active complex with
antithrombin III
Adverse effects: bleeding, GI intolerance, - Enoxaparin, Dalteparin, Tinzaparin
ulcer, bronchospasm, hypersensitivity, - Fondaparinux (synthetic
salicylism polysaccharide
ADP inhibitor Thienopyridines
- Ticlopidine, Clopidogrel, Prasugrel Uses: (HMWH and LMWH)
- Given in for primary and secondary - When coagulation is needed for
prevention of acute myocardial pregnancy (LMWH choice for
infarction (given at least 9 months pregnant women)
after ACS) - When initiating anticoagulant therapy
- Given post- angioplasty - Management of ACS (DOC: LMWH)
- MOA: irreversible inhibitor of P2Y12 - Management of VTE (venous
receptor thromboembolism)
- Adverse effects: Adverse Effects:
Ticlopidine : causes - Bleeding (antidote: Protamine
thrombocytopenia, neutropenia, risk sulfate)
of thrombotic thrombocytopenic - HIT
purpurea - Osteoprosis
Oral
Non-Thienopyridines Oral anti-factor Xa
- Ticagrelor Given for post- - Direct factor Xa inhibitor
angioplasty (to prevent acute - Rivaroxaban, Apixaban
thrombosis) - Used in the management of venous
GIIb / IIIa inhibitors MOA: blocks the G II b / III a receptor to thromboembolism
prevent platelet cross-linking or aggregation - Less adverse effects
Older agents
- Abciximab, Eptifibatide, Tirofiban - VKORC (vitamin K epoxide
reductase) inhibitor

- MOA: inhibits Vitamin K epoxide - Evolocumab, Alirocumab
reductase resulting to inhibition of - MOA: inhibits PCSK9 resulting to increase in LDL receptors
formation of active Vitamin K allowing increase in hepatic and tissue uptake or utilization of
- Examples : Dicumarol, cholesterol
Phenprocoumon, Indanedione - Evolocumab used in the management of hypercholesterolemia
(Phenindione, Anisindiones), that is refractory to other drug
Warfarin
- Adverse effects : Bleeding, RHEUMATOLOGIC DISORDERS
Intracerebral hemorrhage, Abnormal
bone development, Cutaneous
necrosis Inflammatory
Warfarin Autoimmune
- Monitoring parameter: PT-INR Affects the muculoskeletal system
- PT INR: < 2 : underdose | >3 Joints
overdose Muscles
Fibrinolytic Bones
MOA: Activate the fibrinolytic system by conversion of the inactive Tendons and Ligaments
proenzyme, plasminogen into the active enzyme plasmin, that degrades
fibrin
Streptokinase Source: Beta hemolytic streptococci INFLAMMATION
Adverse effects : bleeding, hypersensitivity
A non-sprecific immune reponse against an adverse
Note: stimulus.
- give premeds before running Microbial invasion
infusion: antihistamine, Physical injury
glucocorticoids Purpose: For protection and a part of healing process
- avoid subsequent exposures
APSAC Aminosylated plasminogen streptokinase
activator complex Cardinal Signs of Inflammation
Recombinant t-PA Alterplase, Teneclepase, Reteplase
Used in the management of acute venous
thromboembolism
Within 3 hours of an acute ischemic stroke
Within 30 mins of an acute myocardial
infarction that is ST segment elevated
Pro Coagulant
Vitamin K - 3 forms : Vitamin K1 (phylloquinone
or phytonadione); Vitamin K2 (
menaquinone); Vitamin K3
(menadione)
- Used in the management of bleeding
secondary to Vitamin K deficiency
- Prevent hemorrhagic disorder in the
newborn
Epsilon Tranexamic acid (analogue) Calor Tumor Functio laesa
aminocaproic acid
MOA: inhibits the action of tPA and uPA
Aprotein MOA: directly inhibits plasmin Rubor Dolor
Used in the management of t-PA-associated

bleeding
Autoimmune Diseases
DYSLIPIDEMIA
Arise from overreactive immune response
Abnormal lipid profile T cells
B cells
Adversely target substances and tissues normally present in
the body
Drugs for Dyslipidemia
HMG-COA reductase Inhibitor Rheumatologic Diseases:
- MOA: inhibit the first committed step in cholesterol biosynthesis
- Cholesterol synthesis: peaks at height of sleep Rheumatoid Arthritis affects the synovium
- Examples: (-statin) Arthritis multiple, symmetrical
Long acting (anytime) : Atorvastatin, Rosuvastatin Morning joint stiffness (~1 hour)
Short acting (at bedtime) : Simvastatin, Pravastatin Hand involvement
- Adverse effects: Myalgia, Muscle pain (Myositis) ,
Rhabdomyolysis
Fibric acid derivative
Osteoarthritis most common
- MOA: increase activity of the enzyme lipoprotein lipase (LPL) Non-inflammatory
- LPL: takes up and breaks down triglyceride into fatty acid and Not an autoimmune disease
glycerides or glycerol = lowers serum triglyceride
- Examples: Fenofibrate, Gemfibrozil Systemic Lupus Erythematosus
- Use: Drug of choice in the management of hypertriglyceridemia
- Adverse effects: Myositis, Myalgia, Rhabdomyolysis Butterfly-shaped rash
Nicotinic acid
Photosensitivity
- A form of niacin
- MOA: inhibits synthesis and release of VLDL from the liver Renal complications: Nephritis
- Use: alternative to fibrates for hypertriglyceridemia
- Adverse effects: hepatotoxicity at high doses, flushing Ankylosing Spondylitis
Bile acid binding resins or Bile acid sequestrant Bamboo spine
- Cholestyramine, Colestipol Enthesitis
- MOA: inhibits recycling of bile acids Sacrolitis
- Use: add-ons of statins
Cholesterol transport inhibitor
Drugs/ Agents
- MOA : inhibits intestinal cholesterol uptake is mediated by
NPC1L1-like transporter (Niemann Pick C1-Like-1)
- Ezetemibe ANALGESICS
- Used as an add-on for statins
PCSK9 inhibitors Analgesia loss of pain perception
- Proprotein convertase subtilisin/kexin 9 (PCSK9)
NON-NARCOTICS Anti-inflammatory: 3.2-4 g/day
- MOA : COX inhibition
P-aminophenol Derivatives Anti-pyretic: 0.3-1.2 g/day
- MOA : inhibits response to IL-1 and
Acetaminophen or Paracetamol (Tylenol ®)
cutaneous vasodilation
Weak prostaglandin synthesis inhibitor in the periphery Anti-platelet: NMT 325 mg/day
(COX inhibitor) - MOA : COX inhibition in the platelets 2
Antipyretic activity (Potent aggregant) synthesis inhibition
Lacks anti-inflammtory activity even at higher doses -
1st line for OA - anti-aggregation = bleeding
substitute for Aspirin Anticancer: potential use
- Chronic inflammation (overexpression of
Advantage: safe in pregnant and lactating women and
COX-
among children
Hepatotoxicity Toxicities:
Risk factors: Gastric effects:
dose > 5 mg/kg/day - gastritis, gastrointestinal bleeding (COX-1
pre-existing liver disease inhibition)
concomitant use of CYP1A2 inducers - Treatments:
PPI 1st line
NSAIDs
Misoprostol alternative
Weak organic acids EXCEPT Nabumetone which is Reversible Decrease in GFR:
metabolized into acetic acid derivatives -
inhibits Hypersensitivity reaction:
Prostaglandin - NSAID-induced Bronchial Asthma
synthesis - Treatment: Zileuton, Montelukast, Zafirlukast
Cyclooxygenase (COX) Enzymes - ASA Hypersensitivity Syndrome Nasal
polyposis, Chronic sinusitis
Effects in Serum Uric Acid Levels
- Aspirin, Tolmetin, Salicylates
- < 2g/day: decreased renal excretion of urate
Antagonize uricosuric effect of uricosurics
- C/I in Gout patients taking uricosurics
CNS effects (ASA, Salicylates)
- Mild: salicylism hyperthermia, tinnitus,
hyperventilation
- Severe: acid-base imbalances, hallucination
Cyclooxygenase (COX) Enzymes - Fatal: Respiratory depression
(ASA)
NSAIDS reduced prostanoid - Children: with Fever, Viral infection + ASA
production and thus PGE2 for - Hepatic Failure
instance will be lower - Encephalopathy (brain damage)
Pyrazolones Phenylbutazone
Dipyrone
Sulfinpyrazone Not an NSAID, Uricosuric
Powerful analgesia and inflammatory
Toxicities:
Hemtologic:
Isoforms of COX: - Thrombocytopenia (low platelet), Aplastic
1. COX-1 anemia ,
Agranulocytosis : BEN)
Constitutive Enzymes Nephrotoxicities:
PGs for homeostatic functions (e.g., gastroprotection) - Acute Tubular Necrosis, Anasarca (massive
edema), Nephrotic Syndrome
2. COX-2 Indole Indomethacin
Inducible Enzymes
PGs for inflammation (PGE2) - Blocks COX-1 > COX-2
- High risk of GI effects
Uses:
NSAIDs - To enhance closure of Patent Ductus
Arteriosus)
Non-Selective COX inhibitors - Management of Bartters Syndrome (defect in
Aspirin the reabsorption of electrolyte by the kidney)
Pyrazolones - Treatment of pain in acute gout
Indole Pyrrole Alkanoic Tolmetin
Acid - C/I: Gout
Pyrrole Alkanoic Acid
Phenylacetic True phenylacetates:
Phenylacetic Acid Acids - Sulindac
Fenamates - Alclofenac
Oxicam - Diclofenac
Propionic Acids Acetic acid derivatives:
- Ketorolac
Specific COX-2 Inhibitors - Etodolac
- Nabumetone
Celecoxib
Etoricoxib Sulindac SJS/TEN
Valdecoxib Ketorolac treatment of pain after surgery
Rofecoxib Fenamates Mefenamic acid
- Advantage: less associated to gastric effects Meclofenamate
- Increased risk of acute thrombotic events Flufenamic acid
- Analgesia only
Non-selective COX Inhibitors: - Used for NMT 5 days (acute pain)
- Never given in children
Aspirin Prototype; Irreversible COX inhibitor
- Safest for children: Ibuprofen
Oxicam Piroxicam
Pharmacodynamics :
- Bleeding and ulceration are more likely to
Analgesic: <600 mg/day
happen
- MOA : inhibits pain perception at subcortical
- Blocks COX-1 >>> COX-2
sites of the brain (central) and COX inhibition
- highest risk of GI effect
(peripheral)

Propionic Acids Ibuprofen Hyperventilation
Naproxen Mydriasis
Ketoprofen RhinorrheaHostility
Flurbiprofen Contraindications Head trauma
Pregnancy
- Analgesic and anti-inflammatory D/I with full & partial agonists
- Ibuprofen and Naproxen: additional Antagonistic
antipyretic
- Naproxen: used for fever of malignancy Classifications:
NARCOTICS Opiates
Opioids
Narcosis Based on Sources
Synthetic
Insensibility
Stupor
Opioid Agonists Strong Full Agonists

Based on Mild to Moderate Full Agonist
Papaver somniferum Pharmacodynamics Partial Agonist
Brown gum Opioid Antagonist
Morphine (10%)
Mechanism of Actions: Based on sources
Opiates Natural opium alkaloids
1. Opioid Peptides endogenous Morphine
- Standard comparison as analgesic
Opioid-like pharmacologic properties:
- Undergoes extensive first-pass effect
Endorphins
Enkephalins Codeine
Met-enkephalin - Standard of comparison as antitussive
Leu-enkephalin - Less effective than Morphine
Dynorphins
Thebaine
2. Opioid Receptors - Precursor in the synthesis of Naloxone
Opioids
Majority of opioid-mediated effects
Semisynthetic:
Mu: Heroin
Analgesia - Diacetylmorphine/diamorphine
Euphoria - common drug of abuse
Miosis
Constipation Apomorphine
Respiratory depression - not an analgesic
Kappa: - Dopaminergic: DA reuptake inhibitor; D2 agonist
- Emetic
Additional analgesia in women - Management of Parkinsonism
Delta:
Spinal analgesia Semisynthetic Morphine Derivatives
Modulation of hormone and neurotransmitter release - Hydroxymorphone, Oxymorphone
- 8-12x more potent than Morphine
Opioid Agonists
Mechanism of Action Stimulate the release and mimic the action of Semisynthetic Codeine Derivatives
endogenous opiod peptides - Hydroxycodone, Oxycodone
Actions Central - 8-12x more potent than Codeine
Analgesia Synthetic:
Euphoria Methadone
Miosis - similar efficacy with Morphine
Cough suppression - longer DOA
Respiratory depression - less rapid development of tolerance
Emesis - to wean off patients addicted to Morphine or Heroin
Peripheral Meperidine (aka Pethidine)

Constipation - no cardia or biliary effect
Hypotension - converted to Normeperidine
Bradycardia - used for acute pain only
Histamine release - A/E: seizures
Tocolysis
Biliary contraction Levorphanol
Clinical Uses Analgesics - 5-7x potent than Morphine
Mild Tramadol - D-isomer: Dextrometorphan
Moderate Codeine - Antitussive
Severe Morphine
Management of acute pulmonary Loperamide & Diphenoxylate
edema Morphine - antidiarrheals
Ability to reduce anxiety effect Diphenoxylate
Can lower afterload and preload - causes addiction
Anesthetic adjuncts - co-administer with Atropine
Antidiarrheals
Diphenoxylate Tramadol
Loperamide - mild pain
Antitussives - derivative of codeine
Dextromethorphan
Toxicities Respiratory depression Fentanyl & related drugs
greatest threat - Alfentanyl & Sufentanyl
Increase in Intracranial Pressure - 100x more potent than Morphine
C/I: head trauma
Pentazocine
Tolerance:
- partial kappa agonist
2-3 weeks of chronic use
Physical dependence
withdrawal symptoms:
Frequent yawning

Based on Pharmacodynamics - Management of severe hyperuricemia;
Strong Full Agonists Morphine and related drugs reduce risk of urate stone formation
Fentanyl - Prevent or Management of Tumor Lysis
Heroin syndrome
Methadone - Adverse effect: Rash or SJS-TEN);
Oxymorphone Aplastic anemia; Hepatitis; Renal failure
Hydromorphone Febuxostat - Indication: the same as allopurinol
Meperidine - Used if patient cannot tolerate allopurinol
Levorphanol - Advantage: not associated with SJS-TEN
Mild to Moderate Full Agonist Codeine and related drugs - Adverse effects: increase cardiovascular
Hydrocodone mortality, myocardial infarction
Oxycodone - Contraindication: CAD
Tramadol Xanthine oxidase MOA : facilitate conversion of urate to a more
Partial Agonist Nalbuphine inhibitors soluble product, allantoin.
Butorphanol Recombinant Urate Oxidase
Pentazocine
Buprenorphine Pegloticase
Opioid Antagonist - Treatment of Narcotic - For patient with refractory
poisoning - CI: presence of G6PD deficiency
Rasburicase
Naloxone - Used in patients who are at risk of
Naltrexone developing tumor lysis syndrome
Nalorphine - Management of elevated uric acid levels
Nalmefene - Adverse effects: hemolytic anemi
Levallorphan
DMARDs
GOUT
Disease-modifying antirheumatic drugs
Metabolic disorder Chemically diverse agents
Increase deposition of monosodium urate crystals in the Alter or reverse disease progression
tissue + hyperuricemia (increase of total uric acid in the body Aka SAARDs (Slow acting ARDs)
Signs and symptoms : Full effect: 6 12 months
Acute arthritis :
Cardinal features of inflammation ( rubort, tumor, Classifications:
calor, function laesa) Small molecule drugs
usually monoarticular ( one joint | 1st Nonbiologic Agents
Metarsophalangeal joint)
In elderly women : polyarticular usually arthritic
Large molecule drugs
joint Biologic Agents
Recombinant DNA technology
Chronic gout :
(+) tophus subcutaneous deposit of MSU crystal Nonbiologic Agents
(+) gouty nephropathy form of chronic kidney Methotrexate - 1st line DMARD
disease - MOA: blockade of AICAR transformylase
(+) uric acid stone formation
enhance release of Adenosine
Drugs for Gout - Hence: inhibition of inflammation
Acute Gout - blocks chemotaxis
Pain control - NSAIDs (except aspirin and salicylates) - low dose; higher doses = anticancer
- Drug of choice: short acting and lipid effect
soluble Antimalarials - 2nd line DMARDs
- Indomethacin - Hydroxychloroquine, Chloroquine
- Ibuprofen - MOA: blocks T lymphocyte responses to
- Diclofenac mitogens; inhibits chemotaxis and inhibits
Anti-inflammatory Colchicine DNA & RNA synthesis
- MOA: inhibits microtubule synthesis - T/E: Optic neuritis, cinchonism (tinnitus,
- Adverse effects: hematologic (aplastic headache, dizziness)
anemia, hemolytic anemia, Gold Compounds - Parenteral: Aurothiomalate,
thrombocytopenia); acute hepatitis; renal Aurothioglucose
failure; bloody diarrhea - Oral: Auranofin
- Contraindication: elderly, presence of renal Sulfasalazine - Metabolized to: Sulfapyridine (active for
failure DMARD), 5-aminosalicylate
- Note: Diarrhea is the first indication of (Meselamine: IBD)
toxicity - A/E: Nausea and vomiting, skin rashes
Oral glucocorticoids and discoloration, hematotoxicities
- Prednisone Leflunomide - metabolized to: A77-1726
- For polyarticular arthritis in elderly patients - inhibits dihydroorotate dehydrogenase
Adrenocorticotropic hormone (IM ACTH) - inhibits ribonucleotide synthesis
- For refractory polyarticular acute gout for
elderly patients with renal failure Biologic Agents
Chronic Gout Abatacept - T cell modulating biologic
Hypouricemic therapy - inhibits activation of T cells
- Goal : decrease serum uric acid; <300-360 mmol/L - used as monotherapy or in combination
- Indication: with methotrexate
Acute attacks more than 2 times Rituximab - B cell depleting agent
Stable doses of colchicine and without flares for atleast 2-3 weeks - targets CD20 b lymphocytes = reduced
Commitment for long term therapy inflammation
Uricosuric agents Probenecid - combined with methotrexate
- The only agent used Tocilizumab - inhibits IL-6 mediated signaling
- Indication: if urine uric acid is <600 mg/day - for moderate or severe RA
- Adverse effect: urate stone formation Anakinra - IL-1 neutralizing agent
- Note: ensure that the patients water intake - approved for use in RA (not very
is 1.5L/day effective)
Sulfinpyrazone, Penicillamine - A/E: severe injection, irritation at the site
MOA : blocks xanthine oxidase to inhibit uric acid of injection
formation TNF- - Adalimumab, Infliximab, Certolizumab,
Etanercept, Golimumab
Allopurinol - A/E: Severe infection
- Management of chronic gout

GLUCOCORTICOIDS 2. Renin angiotensin aldosterone system (RAAS)
Role: Long-term BP regulation
2 ways to administered glucocorticoids
1. Systemic (PO or IV) Bradykinin

Management of RA, SLE Angiotensinogen Kininase II or Peptidyl
Life-threatening SLE: pulse therapy of Methylprednisolone Angiotensin I dipeptidase or ACE
(1000 mg IV for 3 days) Resin
Angiotensin II Inactive
kinin
2. Local (Intrasynovial) (4-6 mos) Binds to AT1
fragments
- Direct vasoconstriction
Management of OA that id unrelieved with NSAIDs or - Stimulate synthesis and
Stimuli:
analgesic - release of catecholamines
- Renal hypotension - Stimulate synthesis
release and Aldosterone
CARDIOVASCULAR - Renal hypoperfusion
1. HYPERTENSION Determinants of Blood Pressure

Hydraulic Output: BP = CO x SVR
A. PHYSIOLOGY OF BP REGULATION Where BP =blood pressure
CO = cardiac output
Mechanism of regulations SVR (TPR or PVR) = systemic vascular resistance
Cardiac Output: CO = SV x HR
1. Baroreceptor reflex mechanism Where SV = stroke volume
Role: moment-to-moment BP regulation HR = heart rate
Components: Determinants of Stroke Volume
Affector carotid baroreceptors dependent on the tone
Central integrating region central vasomotor area of the veins and blood volume
Effectors hearts, blood vessel Inotropism (strength of contraction)
Determinants of SVR
Tone of the arterioles
Carotid baroreceptors Determinants of Blood Pressure
Mechanoreceptors Effects on Vascular Tone
Activated when Vasoconstriction
vessel wall is
Endothelin
Heart: Decrease HR
Angiotensin II
Vasodilation
Blood vessels: Vasodilation
Arteriolar 2 activity
Nitric oxide
Bradykinin
Physiologic consequences of change in body position
Activation of
Lying flat on
volume and carotid B. PATHOPHYSIOLOGY OF HYPERTENSION
bed
pressure baroreceptors
Blood Pressure categories

JNC 7 HTN Classifications
Decrease HR, Decrease

Category SBP DBP
Peripheral sympathetic Normal <120 <80
Vasodilation discharge Prehypertension 120-139 80-89
Stage 1 HTN 140-159 90-99
Stage 2 HTN
Sudden upright
Deactivation of
posture
volume and carotid Other Hypertensive Categories
(peripheral
pressure baroreceptors Hypertensive Crisis Urgency no acute TOD nor worsening
vasodilation)
(>180/120) TOD
Emergency w/acute TOD or worsening
TOD
Resistance Despite at least 3 anti-HTN medications
Resumption of Hypertensive including a diuretic
Increase HR, sympathetic
discharge
White Coat Despite 3 months of therapeutic lifestyle
Hypertensive change but ambulatory BP or home BP
Explains Adverse Effects of certain drugs
monitoring <130/80
<160/100)
Preferential blood Masked After 3 months of therapeutic lifestyle
Arteriolar Hypertensive (120- change but w/ ambulatory BP or home BP
Vasodilators Reduced blood 129/<80)
flow to the carotid
Hypertension Gestational HTN
during Pregnancy Onset or after 20 weeks age of
gestation
Must be resolved 12 weeks post-
Deactivated partum/after deliver
Inhibited Chronic HTN
Increase HR: carotid
sympathetic Onset is before 20 weeks age of
Reflex
discharge from the
tachycardia inactive inhibitory gestation
vasomotor area
interneuron Renal Pre-eclampsia
Hypertension in No seizure episodes
Pregnancy MgSO4: prophylactic anticonvulsant
Eclampsia
Seizures
MgSO4: Tx for convulsion

C. CLASSES OF DRUGS FOR HYPERTENSION K+ sparring Diuretics
Classes based Aldosterone antagonists:
on MOA - Spironolactone
Duretics - Eplerenone
Direct NaCl transport inhibitors:
Sympathoplegics - AmilorideTriamterene
Role in HTN - For resistant hypertension associated with
Vasodilators management hyperaldosteronism
- Given with thiazide or loop diuretic to prevent
Arteriolar vasodilators or treat diuretic-induced hypokalemia
Mixed arteriolar and venous dilators Adverse Effects - Hyperkalemia
- Spironolactone: anti-androgenic effects
Angiotensin modifiers gynecomastia
ACE inhibitors - Triamterene: renal formation stone (drug
precipitation)
Angiotensin receptors blockers
Renin inhibitors Carbonic Anhydrase Inhibitors
Calcium channel blockers Structure - Sulfonamide
Examples - Acetazolamide prototype
- Brinzolamide
DIURETICS - Dorzolamide
- Methazolamide
MOA: promote urinary +/- electrolytes - Dichlorphenamide
Classification: based on site of action in the Renal tubule MOA Inhibits the enzyme Carbonic anhydrase, resulting in
the inhibition of the resorption of bicarbonate by the
tubular cells, leading to retention of bicarbonate in the
Summary on site of action tubular
Proximal convoluted tubule - Carbonic anhydrase inhibitors Effect Proximal Convoluted tubule (PCT)
- Osmotic diuretics - Natriuresis
- Xanthines, Acidifying salts - Diuresis
Loop of Henle - Early portion: Osmotic diuretic - Bicarbonaturia
- Late portion: Loop diuretic Ciliary body in the eyes
Distal convoluted tubule - Thiazides - Lowers the production of aqueous humor by
Collecting duct/tubule - Potassium-sparring diuretic the ciliary body
MOA: promoteWith known role in hypertension management: Use - Management of glaucoma
Loop Diuretics - Open angle glaucoma
Thiazode Diuretics - Acute treatment for acute angle closure
glaucoma
K+ sparring Diuretics
Acetazolamide
- used in the management of acute mountain
Loop Diuretics sickness
aka. High ceiling diuretics - management of certain seizure disorder/
Structure Sulfonamide: epilepsy
- Furosemide - management of metabolic alkalosis
- Bumetanide Adverse effects Acetazolamide
Sulfonylurea: - Dermatologic rashes, SJS-TEN
- Torsemide - Hematologic Aplastic anemia,
Phenoxyacetatic acid: Thrombocytopenia, Leukopenia
- Ethacrynic acid Drug interaction - Lithium loss of efficacy
MOA Inhibit NKCC2 (Na-K-2Cl cotransporter) at the thick - Methenamine mandelate reduced activation
ascending limb - Other: metabolic acidosis: increase risk in
Effects Initial effect: peripheral Venodilation patient with COPD
Contraindication Presence of COPD
Diuresis,Natriuresis, Kaliuresis, Calciuresis,
Magnesiuresis Osmotic diuretic
Role in HTN Adjunct in the management of HTN emergency
Example Mannitol
complicated by pulmonary edema
MOA Induce increase osmotic gradient across renal tubule
Adverse Effects Dehydration, hypotension, ototoxicity
(PCT and early LOH) which prevents water
Electrolyte imbalance:
reabsorption at the water permeable regions
- hypokalemia, hyponatremia,
hypomagnesemia Use - Management of intracerebral edema and
Metabolic: increase intracranial pressure
- hyperuricemia, hyperglycemia, dyslipidemia - Management of certain cases of poisoning
Sulfa-associated (sulfonamide, sulfonylurea): and in rhabdomyolysis
- hypersensitivity, SJS-TEN, and other - Induce urinary excretion of metals (eg.,
dermatologic reactions, aplastic anemia and Platinum or Cisplatin)
other hematologic reactions Adverse - Hypovolemic hypernatremia
Effects - Increase risk of pulmonary edema
Thiazide Diuretics
Structures Benzothiadiazides
STMPATHOPLEGICS
- HCTZ (hydrochlorothiazide)
- Chlorothiazide Peripherally acting
Sulfonamide thiazide-like Adrenergic Reserpine + Related agents
- Chlorthalidone neuron blockers - MOA: inhibit vesicular uptake and storage of
- Metolazone catecholamine
- Indapamide Guanethidine + Related agents
MOA Inhibit Na+-Cl- symporter at the DCT MOA: inhibit exocytosis of norepinephrine
Effects: st
1 2 weeks: C/A: management of HTN
- diuresis + natriuresis A/E: postural hypotension
Beyond 2 weeks of therapy: Ganglionic No longer used
- increased vascular blockers
Role in HTN among the 1st line therapies Beta blockers Propanolol, Nebivolol, Atenolol, Metoprolol
management - given at low doses (lower risk of hyponatremia) MOA (antihypertensive effect):
- Block cardiac 1
- given combined with other antihypertensives
Adverse Same as loop diuretics, more prominent hyponatremia - Block 1
Effects at higher doses release
Role in HTN:

- Beneficial among antihypertensive patients Adverse Effect:
with concurrent CAD, anxiety episodes, - Increased intraocular pressure
hypersympathetic stimulation Adverse Effects:
- Hypertensive crisis: Esmolol very short - Common to all: Reflex tachycardia, palpitations, peripheral edema
half-life Mixed Arterial and Venous Dilators
- Hypertensive in pregnancy: Labetalol Sodium MOA:
Adverse effects: (refer to autonomics topic) Nitroprusside - it stimulates nitric oxide
- Rebound HTN and tachycardia if abruptly ----
stopped Vasodilation
Alpha blockers Prazosin, Phentolamine
MOA (antihypertensive effect): Use in HTN:
- Block 1 - Hypertensive emergencies (DOC)
vasodilation Metabolism/Degradation:
Role in HTN management: - metabolized by Hb, O2, Light and yields to
- Hypertension associated with Thiocyanate (Weakness, Disorientation,
Pheochromocytoma Psychosis, Muscle spasms, Convulsions)
- Hypertension among patients with BPH and Cyanide (Metabolic acidosis, Severe
Adverse effects: (refer to autonomics topic) hypertension, Arrhythmias, Death)
- First-dose phenomenon Cautions:
- Protect from light
Centrally acting - Use within 24 hours of preparation
2 Clonidine - Limit duration of infusion to <1hr if given at
agonists MOA and effects: high doses
- Stimulates postsynaptic 2 in peripheral Nitrovasodilators
vessels (same effect as 1)
vasospam ANGIOTENSIN MODIFIERS
- Stimulates ptrsynaptic central 2
Decreased release of central NE ACE inhibitors and Angiotensin Receptor blocker
Role in HTN management: MOA:
- Hypertensive crusis, management of HTN - AT1 receptors
among patients on hemodialysis
Adverse Effects: *ACE is involved in the metabolism of bradykinin (powerful
- Sedation, Depression
- Initial transient increase in BP Use:
- Withdrawal-induced rebound HTN ater 1 or 2 - First line in the management of hypertension (never combine
missed doses ACE-
doses, give Labetalol od drugs for - First line in the management of CHF (unloader)
hypertensive emergency - First line in the management of proteinuria
Adverse effects:
rise in BP followed by peripheral vasodilation and - Hyperkalemia
decrease in BP - Hypotension (especially with ACE-
increase dose)
Methyldopa - ACE-I associated: dry cough or idiosyncratic cough
MOA: Prodrug - ARB associated: Hyperuricemia (losartan)
- - - - Contraindication:
- Presence of bilateral renal artery stenosis
2 - Pregnancy
Use in HTN:
ACE inhibitors MOA:
- management HTN in pregnancy
- blocks ACE/ Kininase II leading to
Adverse Effects:
decreased levels of AT II, increased levels
- Hepatotoxicity at doses >2g/day
of bradykinin (causes vasodilation)
- Sedation, depression
Examples based on Zn binding moieties:
-
- Sulfhydryl Captopril
- Phosphinyl Fosinopril
Guanabenz,Guanfacine
- Carboxyl all the rest
- Share the -adrenoceptors-stimulating
Angiotensin Losartan, Candesartan
effects of clonidine
Receptor MOA:
blocker - blocks binding of AT II to AT1 receptor
VOSODILATORS causing vasodilation due to decrease of AT
II activity
Arteriolar Vasodilators Note: vasodilating effect (ACE-
Hydralazine MOA: Renin inhibitor Aliskiren
- Nitric oxide-mediated vasodilation MOA:
Uses in HTN: - binds to the S3 binding protein and prevents
- HTN in pregnancy renin from binding to angiotensinogen
- Hypertensive crisis Use in HTN: combined w/ ACEi or ARB
Adverse Effect: - Greater BP lowering than ACEi or ARB
- Drug-induced lupus alone
Minoxidil MOA: - DOES NOT improve cardiovascular
- Opening of potassium channels leading to outcomes
hyperpolarization of arteriolar smooth Adverse Effects:
muscle membranes - Increase CV mortality and events in DM
Uses in HTN: patients
- Hypertensive crisis - Rashes, diarrhea, nausea & vomiting
Adverse Effect: - Angioedema (rare)
- Hirsutism/ hypertrichosis
Diazoxide MOA: CALCIUM CHANNEL BLOCKERS
- Opening of potassium channels leading to
hyperpolarization of arteriolar smooth Several medications that disrupt the movement of calcium through calcium
muscle membranes channels
Uses in HTN:
Classification based on structure
- Hypertensive crisis
Dihydropyridines - Amlodipine
Adverse Effect:
(-dipines) - Nifedipin
- Hypoglycemia
- Nimodipine
Fenoldepam MOA:
- Felodipine
- Activation of D1 receptors in arterioles
- Nicardipine
leading to arteriolar dilation and natriuresis
MOA:
Uses in HTN:
- blocks the L-type Ca+ channels in arteriolar
- Hypertensive crisis
vascular smooth muscles

Effect: C. CLASSES OF DRUGS FOR ANGINA PECTORIS
- Arteriolar vasodilation, Reflex tachycardia,
Peripheral edema Nitrovasodilators
Note: intrinsically natriuretic and diuretic
Structure Organic nitrates and nitrites
Non- - Verapamil
MOA Breaks down in circulation to release nitric oxide (NO). It
dihydropyridine - Diltiazem
does this by binding to oxyhemoglobin to release cyanide,
MOA:
methemoglobin and nitric oxide. NO activates guanylate
- blocks the L-type Ca+ channels in arteriolar
cyclase in vascular smooth muscle and increases
vascular smooth muscles and the heart
intracellular production of cGMP
Effect:
Effect At low doses:
- Arteriolar vasodilation, Bradycardia
-
(-inotropism), Peripheral edema
relief)
Note: intrinsically natriuretic and diuretic
Primary mechanism of anti-anginal effect
At high doses:
Classification based on Duration of Action
- Coronary artery vassodilation and peripheral
Intrinsically - - arteriolar dilation
short-acting - Verapamil - Risk: reflex tachycardia
- Diltiazem
Uses - Acute relief of angina pectoris
Intrinsically long - Amlodipine - Management of Prinzmetal angina (high dose)
-acting - Lacidipine
Examples Short acting: NTG, ISDN, amyl nitrite inh.
- Tercanidipine
- Onset of effect: < 1 minute
Modified long - Intrinsically short acting but is formulated as - DOA: 10 minutes
acting modified release products Intermediate acting: NTG SR tablet, ISDN regular tablet
- Adalat GITS (Nifedipine) - DOA: 5-8 hours
- Verapamil XR
- Diltiazem XR Long acting: ISDN extended release, Isosorbide
- Plendil XR (Felodipine) mononitrate, ISDN transdermal
Use: - DOA: > 24 hours
- 1st line in the management of Hypertension
- Nicardipine IV: hypertensive emergency Compound Route DOA
NTG SL Approximately 10 mins
Adverse Effects:
Spray Similar to Sublingual
Consequences of arteriolar vasodilation:
tablets
- Contraindicated in CAD
- All CCBs peripheral edema (capillary congestion) Ointment Effect up to 7 hrs
Myocardial depression: non-DHP TD 8-12hrs intermittent
- Bradycardia, Heart block - Contraindicated in HF and heart blocks therapy
- Gingival hyperplasia PO 4-8 hrs
IV 7-8 hrs (tolerance)
ISDN SL up to 60 mins
2. ANGINA PECTORIS
PO up to 8 hrs
Spray 2-3 mins
A. PATHOPHYSIOLOGY OF ANGINA PECTORIS Chewable 2-2 ½ hrs
Oral Slow up to 8 hrs
Angina develops when there is an imbalance between Release
myocardial oxygen suppy and demand IV 7-8 hrs (tolerance)
Increase myocardial O2 demand ISMN Oral: 12-24 hrs
Reduced myocardial oxygen supply Pentaerythritol SL unknown
Underlying pathology: CAD tetranitrate
Precipitating events: inc myocardial metabolic Adverse Tolerance
requirements effects - Mech:
of thiols,
- Remedy: observe 12-14 hrs nitrate-free interval
Double product: BP x HR
(prn dosing, intermittent dosing)
Headache
Estimates myocardial O2 demand Fatal hypotension with Sildenafil, Tadalafil
Postural hypotension
Types of Angina Pectoris Drug Severe hypotension/ Fatal hypotension if used or given
interaction within 24-48 hours of Sildenafil or Tadalafil use
Acute Coronary Syndrome
Beta- blockers
Chest pain lasting for 20 minutes, not relieved by rest
nitrates Reduce myocardial O2 demand by preventing increase in
HR, arterial pressure and myocardial contractility caused by
Unstable Angina adrenergic activation
No cell death angina - Reduction: exercise > rest
Rest angina Uses - Maintenance therapy in chronic stable angina
New onset angina - Post-myocardial infarction
Crescendo angina A/E and ANS lecture
Chronic Stable Angina Pectoris (CSAP) C/I
Chest pain lasting for 2-5 hours precipitated by
excretion / stress (emotional) Calcium channel blockers
Prinzmetal Angina MOA - Coronary vasodilation
Episodes of angina (vasospasm) in the coronary - Reduce myocardial contractability & BP
arteries Uses - Maintenance therapy in chronic stable angina
- Prinzmetal angina
Avoid use of short acting CCBs
B. APPROACH TO MANAGEMENT OF ANGINA PECTORIS
Miscellaneous Agents
Increase myocardial oxygen supply
Morphine Effects:
Interventional: angioplasty, bypass graft - -induced autonomic
Medical: use of coronary artery vasodilators responses
-
Reduce myocardial oxygen demand preload
Main medical mgmt. of angina pectoris Trimetazidine MOA: partial inhibition of FA oxidation (ischemic
Reducing metabolic demands/requirements of the heart rease oxygen
requirement)
Ranolazine Inhibits the slow Na+ 2+
entry

3. HEART FAILURE
Adverse Effects: tachyarrhythmias
A. UNDERLYING PATHOPHYSIOLOGY OF HEART FAILURE Phosphodiesterase Milrinone
Inhibitors
MOA: Inhibits PDE- III
myocardium Effects: inotropism, vasodilation
Precipitating events: increase in cardiac workload (preload,
afterload) Uses:
Approach Management acutely decompensated chronic HF
Increasing strength of cardiac contraction cute HF
Pharmacologic: inotropism
Adverse Effects:
Surgical: cardiac transplantation - tachyarrhythmias
Reduce the cardiac workload - bronchospasm
Main medical approach to mgmt. - hypokalemia
preload unloaders, - tremors
afterload unloaders - easy bruising
Goals: Calcium Levosimendan
Improve functional capacity NYHA Functional sensitizers
MOA:
Classifications
- sensitizes troponin C to Ca2+dependent
Class I Symptoms with activities beyond regular activities low energy cost during systole
Class II Symptoms with regular activities - sensitization is reduced during diastole
Class III Symptoms on less than regular activities
Class IV Symptoms even at rest relaxation
- opens ATP-dependent K+channels in
Reducing mortality & morbidity myocytes & vascular smooth muscle cells
Non-pharmacologic interventions: activities,
diet/caloric restrictions, fluids, salt intake Advantages:
Pharmacotherapy - NO cardiac myocyte dysfunction,
Necessary interventional procedures arrhythmia, or increase of energy
consumption
B. DRUGS USED FOR HEART FAILURE - Inotropism + unloading effect
Inotropics Uses:
- Acute HF
Cardiac Glycosides
- Acutely decompensated HF
Digoxin MOA: Na+/K+-ATPase inhibition results in reduced
Ca2+ expulsion and increased Ca2+ stored in
A/E
sarcoplasmic reticulum
- Headache, Dizziness, Nausea
- Hypotension
Effects:
- Mechanical: increase strength of cardiac
contraction (inotropism) Non-inotropic: Unloaders, Neurohormonal controllers
- Vasodilators
conduction velocity, inc ACEis & ARBs 1st line therapies for HF
automaticity and arrhythmia
Effect: reduced cardiac preload and afterload
Effects are enhanced by:
- Hypokalemia Dosing (ACEis): start at low dose, titrate q 1-2
- Hypomagnesemia weeks to maximum dose to maximum tolerated
- Hypercalcemia
- Hypoxia
Captopril
Uses - nID: 6.25 mg q 8h
- symptomatic LV dysfunction in patient - MD: 50 mg q 8h
with concomitant atrial fibrillation (AF) Enalapril
- control ventricular rate in pc with AF and - ID: 2.5mg q 24h
HF - MD: 40mg q 24 h
- Adjunct if with persistent signs and Lisinopril
symptoms of HF despite ACEi or ARB - ID: 5mg q 24h
- MD: 40 mg q 24 h
Before starting therapy: Perindopril
- serum K+, Mg2+ and Ca2+ levels should be - ID: 2-2.5 mg q 24h
within normal range - MD: 16-20 mg q 24h
- Adjunct dose based on renal function
Sacubitril Valsartan
Preparations: Tablet (70-75% BA), soft gel - Neprilysin inhibitor prodrug + ARB
capsule (100% BA), injection - MOA:inhibits neprilysin enzyme and
activates BNP receptors
Adverse effects: less likely if serum digoxin - Use:1st line therapy for HF (more
<1mg/mL efficacious than Enalapril)
- Cardiac: arrhythmias ventricular - Adverse Effects:
arrhythmias, junctional arrhythmias Hypotension
- extracardiac: N&V, visual disturbances Hyperkalemia
Renal failure
Management of toxicity Angioedema
- correct electrolyte abnormalities
- use of anti-digoxin antibodies: DigiFab, Hydralazine + ISDN
DigiBind - Effect: preload + afterload unloading
Beta-1 agonists Dopamine, Dobutamine, Isoproterenol - Uses:
alternative to ACEi or ARBafrican
descent: add-on to ACEi or ARB
ATP----cAMP
-III (Inactive AMP) Nesiritide
-
Uses:
- acutely decompensated Chronic HF - Use: acutely decompensated HF
- acute HF - Adverse Effects:

Hypotension B. DRUGS FOR ARRHYTHMIAS
renal failure
arrhythmias (AF, ventricular tachycardia VAUGHAN WILLIAM SINGH CLASSIFICATION OF ANTI-
hypersensitivity ARRHYTHMICS
Diuretics (Loop Indications: Class 1: Na+ Channel Blockers
diuretics, Thiazide - HF w/ evidence of fluid overload:
1A prolong action potential duration, intermediate dissociation
diuretics, K+ peripheral edema, pulmonary congestion
kinetics, may block K+ channels
-sparring diuretics) - K+-sparring diuretics: add-on therapy,
further reduce mortality and morbidity
Procainamide, Quinidine, Disopyramide
Uses: SVTs, VTs, Afs

kg/5 days (loop, thiazides)
Side Effects:
Diuretic resistance: failure to treat volume
- Associated w/ risk of TDP
-160 mg
- Procainamide: drug-induced lupus
- Remedy: Thiazide + Loop
- Quinidine: N&V, cinchonism (tinnitus, vertigo, blurred
Sympatholytics Beta blockers (Metoprolol, Bisoprolol, Carvedilol, vision, diplopia, confusion, delirium) Autoimmune and
Nebivolol) inflammatory syndromes pneumonitis, fever, urticaria,
- benefit: reduce mortality and morbidity in exfoliative rash, sicca syndrome, thrombocytopenic
stable CHF pupura)
- must be given after at least 2 week of
1B Shorten action potential duration, rapid dissociation kinetics
anti-HF treatment to stabilize CHF
- Dosing: start at low doses and titrate
Lidocaine, Phenytoin,Tocainide, Mexiletine
slowly to maximum tolerated dose
Uses: VTs
Metoprolol
- Lidocaine: VTs in the setting of MI or ischemia
- ID: 12.5mg q 24h
- MD: 200mg q 24h
Side Effects
Carvedilol
- Lidocaine: slurred speech, paresthesia, tremors, ataxia,
- ID: 3.125mg q 12h
seizures, delirium
- MD: 25-50mg q 12h
1C Minimal effect on action potential duration, slow dissociation
Bisoprolol
kinetics
- ID: 1.25mg q 24h
- MD: 10mg q 24h
Flecainide, Encainide, Propafenone, Moricizine
Nebivolol
- ID: 1.25mg q 24h
Uses: SVTs, VTs, Afs
- MD: 10mg q 24h
Side Effects:
4. ARRHYTHMIAS - Propafenone: unusual taste, N&V
- Flecainide: increase rate of death and cardiac arrest
A. COMMON ARRHYTHMIAS -MI w/ asymptomatic PVcs and
non-sustained VT, Ventricular arrhythmias; visual
Normal Sinus Rhythm disturbances, dizziness
Class 2: Beta Blockers
Atenolol Effects: Affects predominantly SA and AV nodes
Propranolol (slow-channel tissues) decrease rate of
Esmolol (Bisoprolol automaticity, slow conduction, velocity, prolong
7 metoprolol) refractoriness
Uses: SVTs, prevent ventricular fibrillation in VTs
Contraindications: Bronchial asthma, history of

anaphylaxis
Class 3: K+ Channel Blockers
Amiodarone Effect: Membrane stabilization
Sotalol -
Atrial fibrillation Bretylium automaticity
Ibutilide - Sotalol has beta-blocking effect
Dofetilide Uses:
- SVTs, VTs
- Amiodarone: 1st line for VTs and AF
No visible P waves Adverse Effects
Irregular R-R intervals - Risk of TDP (highest risk w/ sotalol) and
worsening arrhythmias, bradycardia, and
sinus arrest
Supraventricular Tachycardia
- Headache & chest pain
- Amiodarone:
Thyroid dysfunction (related to iodine
content)
Hepatotoxicity
HR >100 beats/min, usually 140-180 bpm, may be up to 300 Pulmonary fibrosis (rare)
bpm Optic neuropathy/neuritis
Ventricular Tachycardia -fatal Class 4: Ca2+ Channel Blockers
Non DHP CCBs Effects:
- Depress Ca2+-dependent action
decrease rate of automaticity, slow

Monomorphic conduction velocity, prolong
refractoriness
- Reduced HR, prolonged PR interval,
negative dromotropism
Uses:
- Primarily for SVTs
Polymorphic torsades de pointes - Dec rate of AF and A flutter
- Verapamil: for left septal or belhassen VT
Miscellaneous Agents
Adenosine MOA:
Atrial tissues
- Activates adenosine-sensitive K+
channels

- Attenuates catecholaminestimulated HYPOTHALAMIC AND PITUITARY HORMONES
contractility and cAMP accumulation
Ventricular tissues Clinical conditions associated with growth hormone
- Negates catecholamine-induced
deficiency and excess states and their mgmt.
triggered activity by inhibiting adelylate
cyclase and cAMP productions GnRH
Use: acute paroxysmal SVT (AVNRT) Hyperprolactinemia
Posterior pituitary (neurohypophyseal) hormones and drug
Dosing: rapid (1-2) secs IV bolus w/ flush
- -2 mins interval GROWTH HORMONE
if still not sinus rhythm)
Adverse Effects: Growth hormone deficiency
- Bronchospasm, SOB, hyperventilation
- Flushing, headache, sweating, Clinical - Childhood: pituitary dwarfism
palpitations manifestation - Adulthood : increase cardiovascular morbidity
(fatigue, weakness, hypoglycemic effects)
MgSO4 MOAS
Inhibits the Mg2+-dependent Na-K ATPase Management 1st line: Growth hormone
blocks voltage-gated Ca2+ channels (espLTCC),
dec activity of rapid inward component of the Growth hormone preparations
delayed rectifier K+ channel - Cadaveric hormone preparation
Effects: - Somatotropin obsolete
- Prolonged AV nodal conduction times, - Adverse effects : Creutz-Jakob disease
prolonged PR and QRS duration (spongiform encephalitis)
Use: TDP preceded by prolonged QT Recombinant growth hormone
- Somatropin
- Somatrem (contains somatotropin with
ENDOCRINE SYSTEM methionine)
- Clinically useful
PHYSIOLOGY OF ENDOCRINE SYSTEM - Adverse effects : hyperglycemia, increase risk of
Diabetes mellitus
Growth hormone excess

Clinical Childhood: pituitary gigantism
manifestation Adulthood: acromegaly
Management Somatostatin and analogues
- Octreotide and Lanreotide
- Inhibits Growth hormone release, Inhibits
gastrin, Insulin glucagon and TSH release
Use :
- Management of neuroendocrine tumor (carcinoid
syndrome)
- Management of refractory watery diarrhea
- Acute control of bleeding in esophageal varices
and PUD
Dopamine agonist
Hypothalamic Anterior Target Organ Peripheral - Bromocriptine, Cabergolide
hormones Pituitary hormones - D2 agonist which inhibits prolactin release and
Hormones GH release associated with hyperprolactinemia
Thyrotropin RH Thyrotropin SH Thyroid gland T3, T4 GH receptor antagonist
(TRH) (TSH) - Pegvisomant (pegylated somatropin antagonist)
Corticotropin RH ACTH Adrenal cortex Cortisol Peglyated/Pegylation reduces drug clearance and
(CRH) improves overall clinical effectiveness
GnRH FSH LH Ovaries Testes Estrogen
Progesterone Gonadotropin releasing hormones (GNRH) & Luteinizing hormone-
Testosterone releasing hormone (LHRH) and Analogues
GHRH Growth Liver Somatomedin C Effects Physiological effect:
Hormone (insulin linked GF) - achieved if you have an intermittent or pulsatile
serum GNRH level (stimulatory effects on
REGULATION OF THE ENDOCRINE SYSTEM FSH/LH)
- increases estrogen, progesterone, testosterone
Circadian Rhythm
Essentially all pituitary hormone rhythms are entrained to Pharmacological effect:
- seen in sustained serum GNRH level ( inhibitory
sleep and the sleep-wake cycle effect in FSH/LH )
Patterns are repeated approximately every 24hrs - decreases estrogen, progesterone, testosterone
Susceptibility to feedback regulation may be related to the Uses Management of hypothalamic hypogonadism (Intermittent
circadian pattern of hormone secretion administration or pulsative dosing)
Some examples:
GH secretion peak at sleep onset Management of hormone excess state (IM depot/
ACTH and Cortisolsecretion peaks in the early morning with Sustained administration/continuous dosing)
- endometriosis (severe dysmenorrhea)
trough at bedtime
- endometrial cancer
- breast cancer
Local regulation - prostate cancer ( increase testosterone)
Example Adverse Inhibitory dosing
Wolff-Chaikoff effect: excess iodide inhibits further effects - Male: feminizing effect
rease T3 and T4 - Female : masculinizing effect
synthesis = hypothyroidism (DOE: 10-14 hrs) *beyond
10-14 hrs, excess iodides will result to increase T3 & T4 POSTERIOR PITUITARY HORMONE
synthesis = hyperthyroidism
Iodine starting material for thyroid hormone (T3, T4) synthesis Oxytocin and Vasopressin
Organification of iodine step in thyroid hormone biosynthesis produced/synthesized in the posterior hypothalamus, stored
and release from posterior pituitary gland
Feedback regulation
Negative feedback: dominant Oxytocin
Positive feedback Initial milk release
LH surge in response to increase levels of estrogen Uterine contraction

Nasal spray (stimulate milk let down) Glucocorticoids
IV infusion (prevent or treat post-partum hemorrhage; labor Effects Physiologic (10-20 mg/day)
induction; 1 hr. infusion) - Metabolism of CHON, fats
Adverse effects: increase risk of uterine rupture (uterine - Enhance response to catecholamines
tetany) Pharmacological ( 20 mg/day)
- Anti-inflammatory
- Immunosuppression
Atosiban - Catabolism of bones and proteins
Oxytocin receptor antagonist - Inhibition of cell division
Decrease uterine contraction |Prevents pre-term labor; MOA
Tocolytic forming glucocorticoid-glucocorticoid receptor complex
Vasopressin genes
- 1st part: binds to DNA and activates +GRE
ADH -
prevents diuresis inflammatory mediators
Effect: - Other effect: binds to DNA -GRE results to
V1 receptor: blood vessels and vasoconstrictor transrepression
V2 receptor: distal tubule and translocation of aquaporin - mediators
in to cell membrane resulting to water reabsorption Examples Short acting
- Prednisolone, Prednisone,
Vasopressin deficiency Methylprednisolone, Hydrocortisone (cortisol)
Intermediate acting
Diabetes insipidus - Fluprednisolone, Triamcinolone,
- Signs/Symptoms: polyuria, polydipsia, diluted urine Paramethasone
(hypoosmolar), hypernatremia Long acting
Central Central organ problems - Betamethasone, Dexamethasone
Diabetes True ADH deficiency Uses Management of inflammatory diseases
insipidus Management of dermatologic disease
(Pituitary DI) Management : Management of auto-immune disease
Vasopressin Prevents tissue organ rejection
- Non selective V1 and V2 receptor agonist Management of cancer (prednisolone/prednisone)
Desmopressin Anti-emetic (dexamethasone)
- Selective V2 receptor agonist
Adverse effects Cushing's syndrome (moon face, buffalo hump,
- Kidney: decreases water excretion
thinning of skin, easy bruising, cushing's ulcer,
- Used for hemophilia A and Wille brand factor
hypokalemia, proximal myopathy, poor wound healing
disease
activity, risk of osteoporosis, growth retardation)
Nephrogenic Normal or increased levels of ADH but V2 receptors are
Diabetes non-responsive HPA Axis suppression (adrenal crisis or Addison's
insipidus disease) hypotension, abdominal pain, death
Management : - Prevention: taper the dose slowly;
- 1st line: Thiazide Glucocorticoid should not be abruptly
- Alternative : Indomethacin withdrawn if taken for more than >10-14 days
Vasopressin excess Mineralocorticoids

SIADH (syndrome of inappropriate antidiuretic hormone) Effects Physiologic = Pharmacologic
Signs and - Hypovolemia - Reabsorption of Na, H2O, HCO3
Symptoms - Hypertension - Secretion of Cl, H, K
- Hyponatremia
- Concentrated urine (hyperosmolar Hyperaldosteronism
Management Acute SIADH - Na & H2O retention, HTN
- IV hypertonic saline - Hypochloremic metabolic alkalosis
Chronic SIADH - Hypokalemia
- Demeclocycline most photosensitizing Hypoaldosteronism
tetracycline - Hypotension
Vasopressin receptor antagonist - Hyperchloremic metabolic acidosis
- Conivaptan non selective V1 and V2 receptor - Hyperkalemia
blocker Examples Deoxycorticosterone acetate
- Tolvaptan selective V2 receptor antagonist - Precursor of aldosterone
Prolactin Fludrocortisone
- Promotes lactation - Synthetic aldosterone
Prolactin deficiency Impaired lactation - Has both glucocorticoid and mineralocorticoid
Hyperprolactinemia Due to decrease transport of dopamine activity
Signs and symptoms : Spironolactone, Eplerenone
- Women: amenorrhea, galactorrhea - Mineralocorticoid antagonist
- Men: loss of libido, infertility
Management: Bromocriptine (Dopamine agonist) THYROID HORMONE
ADRENOCORTICAL HORMONE PHYSIOLOGY AND REGULATION
PHYSIOLOGY AND REGULATION Thyroid Gland 2 sets of hormones

Thyroid hormones
Adrenal glands consist of 2 physiologically distinct organs: L-T3 (levo triiodothyronine)
adrenal cortex (90%), adrenal medulla (10%) 99.8% protein-bound, 0.2% in free form
Adrenal cortex T1/2 = 1.5 days
Zona glomerulosa mineralocorticoid 10-fold greater affinity for nuclear thyroid hormone
(aldosterone) receptor
Zona fasciculata glucocorticoid (cortisol) 3-4x more potent than T4
Zona reticularis sex hormone Responsible for most of the effects of thyroid
Primary endogenous hormones hormone
Glucocorticoid: cortisol L-T4 (levothyroxine)
Mineralocorticoid: aldosterone 99.98% protein-bound to TBG (thyroxine-binding
Regulation globulin), 0.02% in free form
Glucocorticoids: HPAA Axis, Circadian Rhythm T1/2 = 7 days (3-4 days if hyperthyroid, 9-10 days
Mineralocorticoids: RAAS if hypothyroid)
Physio & regulation GCs Calcitonin

CLINICAL CONDITIONS PANCREATIC HORMONES
Hypothyroidism DIABETES MELLITUS

Primary hypothyroidism High TSH; thyroid gland has defect
Secondary hypothyroidism Low TSH; central organ defect Types of DM
Both low T3, T4
Type I DM absolute lack of insulin
Thyrotoxicosis & Hyperthyroidism Previously known as insulin-dependent DM
Primary hyperthyroidism -Low TSH; thyroid gland is defect Due to destruction of B-cells in the pancreas (autoimmune)
Secondary hyperthyroidism high TSH; Central organ is Age of onset: < 30 years old
defect At the time of diagnosis, patient is not obese
Both high T3,T4 Management insulin for survival
Thyrotoxicosis: excess thyroid hormones
Causes: hyperthyroidism, exogenous thyroid hormone Type II DM relative lack of insulin
Hyperthyroidism: excessive activity of the thyroid gland Previously known as insulin-non-dependent DM
Age of onset: .35 years old
At the time of diagnosis, patient is already obese
Hypothyroidism
Causes Latrogenic/ Post-procedural, Thyroiditis (sequela) Type III DM other causes
Iodine deficiency, drug-induced (amiodarone)
Signs and Hypometabolism, weight gain despite reduced appetite,
Chronic pancreatitis
symptoms fatigue, decreased sweating
Hypoactivity, slow speech and movement, increased
sleeping time Type IV DM Gestational DM
Forms Congenital: Occurs during pregnancy
- cretinism Resolves after giving birth but increase risk of acquiring DM
Severe form:
- myxedema coma Complications of DM
Diagnosis elevated serum TSH Retinopathy
Management Liothyronine (T3)
Nephropathy
- Triiodothyronine
- For emergency state (Myxedema coma)
Peripheral neuropathy
Levothyroxine (T4) Diabetic ketoacidosis
- Thyroxine
- Maintenance treatment PATHOPHYSIOLOGY OF DM
Liotrix (T3 and T4)
Common Signs & Symptoms:
Hyperthyroidism Polyuria
Signs and - Hypermetabolic, Hyper sympathetic, Weight Polydipsia
symptoms loss, Frequent diarrheal, Heat intolerance and Polyphagia
profused sweating Weight loss
- Increase irritability, Palpitation, Tachycardia
Metabolic disorder w/phenotype of chronic hyperglycemia
Causes - Auto immune disease (Graves disease)
- Solitary hyperfunctioning nodule Diagnosis
- Thyroiditis inflammation of thyroid gland; Symptoms of diabetes plus random blood glucose conc
leakage of T3 and T4 into the circulation
- Amiodarone ( after 10-14 days of use)
- Liothyronine and Levothyroxine 2-
Management Thioamide during an oral glucose tolerance test
- Propylthiouracil, Methimazole, Carbimazole
- MOA: inhibits peroxide oxidase; inhibits
peripheral conversion of T4 into T3
Glycated Hemoglobin Test, Glycohemoglobin
- Adverse effects: reversible hepatitis (PTU), Pre-diabetes
cholestatic jaundice (methimazole) , Diagnosis
agranulocytosis (PTU and methimazole) Random blood glucose conc between 140-199 mg/dL
Fasting plasma glucose between 100 to 125 mg/dL
Radioactive iodine 2-hour plasma glucose from 140-199 mg/dL during an oral
- I-131 ( therapeutic); I-125 (diagnostic) glucose tolerance test
- MOA: emits beta particles that causes oxidation
of the thyroid cells = cell destruction HbA1c between 5.7% and 6.4%
- Complication: hypothyroidism
- CI : pregnant and lactating DM Management: Glycemic Control Goals
- Use : for hypothyroidism associated w Preprandial CBG 80 130 mg/dL
disease and hyperfunctioning nodule Postprandial CBG < 180 mg/dL
- Note: should be freshly prepared; patient should
be quarantined for 48-72 hrs.
HbA1c <6.5%
Beta blockers Drugs

- Propranolol, Metoprolol, Atenolol
- MOA: inhibit peripheral conversion of T4 into T3 Insulin
- Use: management of symptomatic - Secreted by the beta cells of the pancreas
hyperthyroidism; adjunct in RA-I therapy; - Co-secreted with amylin
management of thyroiditis - Storage form: Hexamer
- Active form: Monomer
Radiocontrast drugs MOA
- Ipodate, Iopanoic acid - Insulin binds to insulin receptors
- MOA: inhibits peripheral conversion of T4 into - Stimulates the enzyme glucokinase (1st enzyme in glycolysis or
T3 glucose metabolism)
- Promotes translocation of glucose transporters (GLUT 2, GLUT 4)
Dexamethasone into the cell membrane
- Steroid Classification
- Has an immunosuppressant effects Based on Animal source
- MOA: inhibits conversion of T4 into T3 source - Bovine, porcine
- More immunogenic
Recombinant insulin
- Less immunogenic
Based on Native insulin
structure - No modification on endogenous insulin

- Regular insulin, Neutral protamine Hagedorn Examples Repaglinide
(NPH) / Isophane insulin, Insulin Zn suspension Nateglinide
Modified insulin Use Control of post prandial hyperglycemia
- Addition of amino acid or fatty acid Adverse Hypoglycemia
- Insulin lispro, Insulin aspart, Insulin glulisine, effects Weight gain
Protamine lispro, Protamine aspart, Insulin Biguanides
glargine, Insulin detemir, Insulin degludec MOA:
Based in use Demand insulin - D production of glucose via activation of AMP-
- To control post-prandial hyperglycemia activated protein kinase (AMPK)
Basal insulin - Stimulate glycolysis in peripheral tissues
- To control blood sugar levels throughout the day - Inhibit glucagon secretion and action
Based on Ultra short acting - Reduce glucose absorption
duration of - Onset: 5 mins Examples Phenformin
action - Peak: 0.5 -1.5 hrs Metformin Magic bullet drug for DM
- DOA: 1-3 hrs Use Only drug for pre-diabetes
- Drug of choice for type II DM especially in obese patients
- Lispro, Aspart, Glulisine Adverse Weight loss
- Timing of administration: before/ after meal effects Common: diarrhea, GI disturbance, lactic acidosis
- Use: control post-prandial hyperglycemia Phenformin: withdrawn due to lactic acidosis
- Route: SQ Alpha-glucosidase inhibitor
MOA:
Rapid and Short acting Insulin
-
- Onset: 30 mins
of oligosaccharides, trisaccharides & disaccharides
- Peak: 1-3 hrs
Examples Miglitol
- DOA: 3-4 hrs
Acarbose
- Regular insulin (hexamer form)
Voglibose
- Timing of administration: 30 mins before meals
- Use: control post-prandial hyperglycemia Uses Control post-prandial hyperglycemia in T2DM
- Route: SQ, IV Timing of Immediately before meals (at first bite)
intake
Intermediate acting Adverse GI: flatulence, diarrhea, abdominal pain, ileus
- Onset: 1-4 hrs effect
- Peak: 3-4 hrs Thiazoldinediones
- Administration: 10 hrs MOA:
- Protamine lispro, Protamine aspart, Neutral - Binds to PPARy and stimulates the receptor. The PPARy binds to
protamine Hagedorn (NPH) RXR and binds to the DNA and causing transcription of insulin-
- Timing of administration: twice a day pre sensitivity genes
breakfast and pre dinner Example Pioglitazone, (Rosiglitazone)
- Use: provide basal insulin requirements Adverse Inc CV mortality (Rosiglitazone)
- Route: SQ Effect Inc risk of bladder cancer (Pioglitazone)
Hepatic failure (rare)
Long acting Edema, anemia
- Onset: 1-4 hrs Amylin Analog
- Peak: peak less MOA:
- Duration: 24 hrs - Decrease glucagon release
- Timing of administration: once a day pre- - Increase insulin release
breakfast - Increase peripheral response to insulin
- Use: provide basal insulin requirements Example Pramlintide
Adverse effects: Use Given SC as add-on to insulin
Hypoglycemia Adverse Increase risk of hypoglycemia
- Management: proper timing of administration, give glucose effect
supplements Incretin-mimetics
- Awake: glucose tablets or supplements MOA:
- Unconscious: IV D50W -
Lipodystrophy increase insulin release, decrease glucagon release
- Fat deposition Rationale Response to oral glucose load in DM: increasein insulin,
- Management: rotate injection site increase in glucagon
GLP-1 Exenatide
Insulin secretagogues agonist Lixisenatide
MOA Liraglutide
- Blocks ATP-sensitive K+ channel causing depolarization that
results Ca2+ influx and enhance insulin release from the Route of Administration: SC
pancreatic -cells Dipeptidyl Saxagliptin
Sulfonylureas peptidase Linagliptin
MOA: IV inhibitor Vildagliptin
- Inhibit pancreatic release of glucagon, increase insulin receptor (-gliptins) Sitagliptin
binding, decrease hepatic extraction of insulin
Examples 1st gen less toxicity Route of Administration: PO
- Chlorpropramide: has the longest half-life, not Adverse - Increase hypoglycemic episodes w/ OHAs or
used as an initial treatment effects insulin
- Tolbutamide: most cardiotoxic, shortest half-life, - Hypersensitivity rxns, angioedema, anaphylaxis,
preferred for elderly SJS-TEN
- Tolazamide - GI: nausea & vomiting, colitis, pancreatitis
- Acetazolamide - URTI, nasopharyngitis
- Weight loss
2nd gen most potent Sodium-Glucose transporter 2 inhibitors (SGLT-2)
- Gliclazide MOA:
- Glibenclamide (Glyburide) - Inhibits SGLT2 (promotes reabsorption of glucose into the blood).
- Glipizide GLUT-2 will be excreted into the urine
- Glimepiride Examples Canagliflozin
Timing of 15-20 mins before breakfast (dinner if short-acting) Dapagliflozin
intake Empagliflozin
Adverse - Hypoglycemia Adverse - Pain in urination
effects - Blood dycrasia and sulfonamide-associated A/E effects - Oral thrush
(1st gen) - Risk of fungal infection
- Weight gain - Urinary tract infection
- Disulfiram-like effects (1st gen SFU, and Glipizide) Remedy Increase amount of water consumption
Meglitinides
- (-glinide)
- rapid onset
- short duration of action

GLUCAGON
PHYSIOLOGY
Synthesized in & released from the alpha cells of the

pancreatic islet of Langerhans
MOA: binds to its receptors & stimulates adenylyl cyclase to
convert ATP to cAMP
Effects:
Liver cells: glycogenolysis, gluconeogenesis,
ketogenesis
Cardiac cells: inotropism, chronotropism
Uses:
Severe hypoglycemia mgmt.
Reversal of cardiac effects of -blocker toxicity
Adverse Effect:
Minimal: transient N&V
BONE MINERAL HOMEOSTASIS
Regulation of Calcium & Phosphate levels
Calcium & Phosphate are source from diet, once taken up it

will be absorbed in the small intestine.
Once absorbed it will enter in the systemic circulation as
calcium & phosphate
From the systemic circulation, it will be taken up inside the
bone where it is stored
Hormone Effect Too high levels will

result to:
Parathyroid (+) osteoclastic bone Hypercalcemia,
hormone (PTH) resorption hypophosphatemia
(-) reabsorption of PO4 in
the proximal tubule
Vitamin D (+) absorption of Ca & PO4 Hypercalcemia,
hypophosphatemia
Calcitonin (-) osteoclastic bone Hypercalcemia,
resorption hypophosphatemia
Cortisol (-) vit D Hypercalcemia,
hypophosphatemia
Estrogen (-) PTH bone resorption Hypercalcemia,
activity hypophosphatemia
Agents affecting bone homeostasis
Bone Matrix: organic matrix (mainly type I collagen) +

mineral phase (calcium hydroxyapatite)
Bone undergoes regular remodeling
Involved cells: osteoblasts, osteoclasts
Osteoblast: synthesize & secrete organic matrix &
regulate mineralization
Osteoclast: resorb bone matrix

4 2-Pharmacology

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4 2-Pharmacology

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MODULE 4

1. Diagnostic agents drugs being given primarily to determine the

2. Replenishers given to supplement lacking endogenous

AUTONOMIC PHARMACOLOGY Parts of the Synapse

A. ANATOMY AND PHYSIOLOGY OF THE ANS - Synthesis, storage and

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Pre-synaptic Axon terminal B. SYMPATHETIC DRUGS

Enteric Nervous System

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Dopaminergic1 Receptor (Gs-linked)

Dopaminergic2 Receptor (Gi-linked)

The vesicular monoamine transporter (VMAT) is responsible for the transport

Dopaminergic (D) Receptors High potency in activating and receptors

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Tocolytics Accidental local infiltration of alpha agonists and

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Nadolol and Timololmore potent than Propranolol

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Muscarinic (M) Receptors:

Nicotinic Receptors: Indications

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Classifications - anti nicotinic agonist MOA: blocks Nm receptor

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Use: Management of associated with Locations:

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Antagonists DRUGS THAT ACT IN THE CENTRAL NERVOUS SYSTEM

Also known as nerve cells, sends and receive signals

Actions GABA Gamma Amino Butyric Acid

Drug may alter - Directly proportional with D2 receptors affinity

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Neuroleptic malignant syndrome (NMS) MOOD DISORDERS

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Lithium DOC for euphoric mania

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Benzodiazepines -zepam; -zolam

5. Management of bipolar disorder Status epilepticus

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Used in the management of t-PA-associated

Powerful analgesia and inflammatory

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Opioid Agonists Strong Full Agonists

Peripheral Meperidine (aka Pethidine)

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1. Systemic (PO or IV) Bradykinin

1. HYPERTENSION Determinants of Blood Pressure

Blood Pressure categories

Decrease HR, Decrease

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Uses: SVTs, VTs, Afs

Uses: SVTs, prevent ventricular fibrillation in VTs

Contraindications: Bronchial asthma, history of

decrease rate of automaticity, slow

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Growth hormone excess

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